Affinage

HAS2

Hyaluronan synthase 2 · UniProt Q92819

Length
552 aa
Mass
63.6 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HAS2 is a plasma membrane-resident glycosyltransferase that polymerizes UDP-GlcNAc and UDP-glucuronic acid into high-molecular-mass hyaluronan, functioning as a central hub linking extracellular matrix production to cell migration, epithelial-mesenchymal transition, skeletal morphogenesis, cardiac valve formation, and tumor progression. Its catalytic activity and plasma membrane residence require specific post-translational modifications — ubiquitination at K190 for enzymatic function, phosphorylation at T110 for ER-to-PM trafficking, O-GlcNAcylation at S221 for protein stability, and AMPK-mediated T110 phosphorylation as an inhibitory switch — while autophagic degradation via ATG9A provides an additional layer of turnover control (PMID:30394292, PMID:21228273, PMID:32084457). HAS2 transcription is regulated by converging pathways including NF-κB (cytokines), TGFβ/SMAD4/p38, cAMP (prostaglandins), PI3K/Akt, JAK2/STAT3 (UDP-glucose/P2Y14), and a cis-acting antisense lncRNA HAS2-AS1 that remodels chromatin at the HAS2 promoter downstream of O-GlcNAcylation and NF-κB (PMID:25183006, PMID:20522558, PMID:24847057, PMID:31489963). HAS2-driven HA synthesis promotes Rac1-dependent cell migration, TGFβ-induced EMT partly through cell-autonomous suppression of TIMP-1 and activation of FAK signaling, aggrecan retention in cartilage pericellular matrix, and endocardial cushion formation; in vivo, conditional Has2 deletion causes severe skeletal defects and loss of joint cavitation, while transgenic overexpression of naked mole-rat HAS2 extends murine lifespan and reduces cancer incidence through attenuated inflammation (PMID:14729574, PMID:23108409, PMID:22016393, PMID:19633173, PMID:27094859, PMID:37612507).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Whether HAS2-driven HA synthesis per se could promote tumorigenesis was unknown; forced HAS2 expression in fibrosarcoma cells directly increased HA production, anchorage-independent growth, and xenograft tumor formation, establishing HAS2 as an oncogenically sufficient HA synthase.

    Evidence Stable HAS2 transfection in HT1080 cells, soft-agar and nude mouse xenograft assays

    PMID:10070975

    Open questions at the time
    • No loss-of-function control
    • Mechanism linking HA to proliferation not defined
    • No comparison with HAS1 or HAS3
  2. 2002 High

    It was unclear whether HA's cell-biological effects required ongoing HAS2-mediated synthesis or merely the presence of extracellular HA; bidirectional HAS2 manipulation in keratinocytes showed that the dynamic synthesis process — not exogenous HA — controls lamellipodia extension, migration, and cell cycle entry.

    Evidence Stable Has2 sense/antisense keratinocyte lines, wound assay, exogenous HA and hyaluronidase controls

    PMID:12186949

    Open questions at the time
    • Molecular mediator between HA synthesis and lamellipodia signaling not identified
    • Single cell type tested
  3. 2004 High

    The downstream signaling effector of HAS2-produced HA in driving cell migration was identified: genetic epistasis in zebrafish placed Has2 upstream of Rac1 activation for lamellipodia formation during gastrulation, establishing HA as an autocrine migration signal rather than a passive structural component.

    Evidence Morpholino knockdown and epistasis with CA/DN Rac1 in zebrafish embryos, live lamellipodia imaging

    PMID:14729574

    Open questions at the time
    • HA receptor mediating Rac1 activation not identified in this system
    • Whether this pathway operates in mammalian cells not tested
  4. 2004 High

    The upstream signals controlling HAS2 transcription began to be mapped: prostaglandins acting through EP2/IP receptors and cAMP signaling were shown to specifically induce HAS2 mRNA and HA secretion in arterial smooth muscle cells.

    Evidence Receptor-selective agonists, cAMP analogues, HAS2-specific siRNA, HA ELISA in human arterial SMCs

    PMID:14752026

    Open questions at the time
    • Transcription factor binding to HAS2 promoter not defined
    • cAMP-responsive element in HAS2 promoter not mapped
  5. 2009 High

    The in vivo requirement of Has2 for skeletal development was established: conditional Has2 deletion in limb mesoderm caused severe skeletal shortening, growth plate disorganization, failed hypertrophic differentiation, absent secondary ossification, and defective joint cavitation, with reduced aggrecan retention.

    Evidence Conditional knockout (Has2 floxed × Prx1-Cre), skeletal staining, histology, immunostaining in mouse

    PMID:19633173

    Open questions at the time
    • Whether HA acts through specific receptors or as a structural scaffold in cartilage not resolved
    • Has2 versus Has1/Has3 contribution not separated
  6. 2010 High

    NF-κB was identified as a critical transcriptional regulator: proinflammatory cytokines induced HAS2 mRNA via NF-κB in endothelial cells, and HAS2 siRNA abolished monocyte adhesion, linking inflammatory signaling to HAS2-dependent immune cell recruitment.

    Evidence Cytokine treatment, NF-κB inhibition, HAS2 siRNA, monocyte adhesion assay in HUVECs

    PMID:20522558

    Open questions at the time
    • Direct NF-κB binding to HAS2 promoter not shown in this study
    • Contribution of other HAS isoforms not excluded
  7. 2011 High

    Multiple discoveries converged to define HAS2 regulation and function in migration/invasion: AMPK directly phosphorylates T110 to inhibit HA synthesis; HAS2 knockdown in metastatic breast cancer cells blocked invasion via TIMP-1 induction and FAK dephosphorylation; miR-23 was shown to directly target Has2 mRNA controlling cardiac cushion differentiation; and the HAS2–HYAL2–CD44 system generates motogenic LMW-HA fragments.

    Evidence In vitro kinase assay identifying T110, AMPK KO cells, siRNA with invasion/rescue assays, miR-23 gain/loss in zebrafish, chemokinesis assays with siRNA/rescue

    PMID:21228273 PMID:21743962 PMID:21778427 PMID:22016393

    Open questions at the time
    • How AMPK-mediated T110 phosphorylation mechanistically blocks enzymatic activity not structurally resolved
    • TIMP-1 regulation mechanism by HAS2 not fully defined
  8. 2011 High

    Genetic epistasis in zebrafish placed Has2 downstream of Nephronectin and BMP4 signaling in cardiac valve formation, defining its position in the developmental signaling hierarchy for AV canal differentiation.

    Evidence Double morpholino knockdowns (Npnt + has2), BMP inhibition, in situ hybridization in zebrafish

    PMID:21937601

    Open questions at the time
    • Direct transcriptional regulation of has2 by BMP-activated transcription factors not demonstrated
    • Mammalian validation lacking
  9. 2012 High

    TGFβ was shown to upregulate HAS2 via Smad/p38 MAPK to drive EMT, but critically, HAS2 knockdown blocked EMT and migration independently of extracellular HA, revealing a cell-autonomous intracellular function of HAS2 in epithelial plasticity.

    Evidence TGFβ treatment, HAS2 siRNA, Smad/p38 inhibitors, hyaluronidase/CD44 antibody controls, EMT markers in mammary epithelial cells

    PMID:23108409

    Open questions at the time
    • The intracellular mechanism by which HAS2 promotes EMT independently of extracellular HA remains uncharacterized
    • Whether intracellular HA or a non-catalytic HAS2 function is responsible is unclear
  10. 2013 High

    Substrate kinetics were defined: HAS2 requires intermediate UDP-GlcNAc concentrations for activity (unlike HAS1 which needs ~10-fold more or HAS3 which is active at minimal levels), and transfected HAS2 measurably depletes cellular UDP-sugar pools, establishing metabolic coupling.

    Evidence HAS1-3 transfection in COS-1, glucosamine supplementation, HPLC UDP-sugar quantification

    PMID:23303191

    Open questions at the time
    • No purified enzyme kinetics
    • How UDP-sugar depletion feeds back on cellular metabolism not explored
  11. 2014 High

    The epigenetic regulation of HAS2 via its natural antisense transcript HAS2-AS1 was decoded: O-GlcNAcylation recruits NF-κB p65 to the HAS2-AS1 promoter, and HAS2-AS1 remodels chromatin at the HAS2 promoter through histone acetylation, establishing a metabolic-epigenetic axis controlling HA production.

    Evidence O-GlcNAc induction, HAS2-AS1 siRNA, NF-κB p65 ChIP, chromatin accessibility/acetylation assays

    PMID:25183006

    Open questions at the time
    • Chromatin remodeling complex recruited by HAS2-AS1 not identified
    • Whether HAS2-AS1 operates in all cell types unclear
  12. 2014 High

    A new transcriptional input was mapped: extracellular UDP-glucose acting through the P2Y14 receptor activates JAK2/STAT3; phospho-STAT3 directly binds the HAS2 promoter to induce transcription, connecting purinergic danger signaling to HA production.

    Evidence UDP-glucose treatment, JAK2/STAT3 inhibitors, ChIP for pY705-STAT3 on HAS2 promoter in keratinocytes

    PMID:24847057

    Open questions at the time
    • Specific STAT3 binding element in HAS2 promoter not mapped
    • In vivo relevance of UDP-glucose/P2Y14 axis not tested
  13. 2015 High

    HAS2 was shown to function not as an isolated enzyme but within homo- and heteromeric complexes with HAS1 and HAS3, detected by FRET and PLA at both Golgi and plasma membrane; HAS1 co-expression attenuated HAS2/HAS3-driven HA output, suggesting stoichiometric regulation.

    Evidence FRET, acceptor photobleaching, proximity ligation assay, N-terminal domain mutagenesis, HA synthesis assays

    PMID:25795779

    Open questions at the time
    • Stoichiometry and structural basis of HAS complexes unknown
    • Whether complex composition changes with physiological stimuli not tested
  14. 2016 High

    The mechanism by which HAS2-produced HA retains aggrecan was directly demonstrated: CRISPR Has2-KO chondrocytes failed to assemble pericellular matrices or retain exogenous aggrecan, and HAS2 re-expression fully rescued both, proving HA is the essential scaffold for proteoglycan organization.

    Evidence CRISPR/Cas9 Has2 KO in rat chondrosarcoma, particle-exclusion assay, adenoviral HAS2 rescue

    PMID:27094859

    Open questions at the time
    • Whether specific HA chain length is required for aggrecan retention not determined
    • Link protein involvement not addressed
  15. 2018 High

    A comprehensive post-translational modification code for HAS2 was defined: ubiquitination at K190 is required for catalytic activity and PM residence, T110 phosphorylation is required for ER-to-PM trafficking, and O-GlcNAcylation at S221 stabilizes the protein; K190R acts as a dominant-negative, and PM residence (but not HA synthesis) drives extracellular vesicle shedding.

    Evidence Site-directed mutagenesis (K190R, T110A, S221A/D/E), TIRF/confocal microscopy, cell-surface biotinylation, photo-conversion pulse-chase

    PMID:30394292

    Open questions at the time
    • How ubiquitination at K190 activates catalysis mechanistically unclear
    • Whether these PTMs are co-regulated or independent in physiological contexts not resolved
    • No structural model of HAS2 available
  16. 2018 High

    HAS2-AS1 was positioned as essential for TGFβ-induced EMT: TGFβ activates Has2as expression via Smad and non-Smad pathways, and Has2as knockdown abrogated EMT markers and cancer stemness, functioning in parallel with Hmga2 to maintain the mesenchymal state.

    Evidence Has2as siRNA, TGFβ/Akt/Erk inhibitors, CD44/Hmmr knockdown, stemness marker analysis in breast cancer cells

    PMID:30194979

    Open questions at the time
    • Direct molecular mechanism by which HAS2-AS1 maintains stemness not defined
    • Whether HAS2-AS1 acts solely through HAS2 regulation or has independent targets unclear
  17. 2019 High

    HAS2 overexpression was shown to cell-autonomously reprogram chondrocyte metabolism from glycolysis toward oxidative phosphorylation and suppress procatabolic markers (MMP3, MMP13) independently of paracrine HA signaling to neighboring cells.

    Evidence Inducible adenoviral HAS2 overexpression, co-culture of transduced/non-transduced chondrocytes, Seahorse metabolic flux analysis

    PMID:31270213

    Open questions at the time
    • Whether metabolic shift is caused by UDP-sugar depletion or intracellular HA signaling not determined
    • Mechanism of TIMP-1/MMP regulation not fully elucidated
  18. 2020 High

    A new degradation pathway was identified: HAS2 protein is turned over by autophagy via interaction with ATG9A; mTOR inhibition, nutrient deprivation, or pro-autophagic ECM fragments trigger HAS2 degradation, reducing HA output and angiogenic sprouting; chloroquine stabilized HAS2 in vivo.

    Evidence Super-resolution microscopy of HAS2-ATG9A co-localization, autophagy inducers, chloroquine in vivo, ex vivo sprouting assay in endothelial cells

    PMID:32084457

    Open questions at the time
    • Whether ATG9A directly binds HAS2 or acts through an adaptor not determined
    • Selectivity of autophagic degradation for HAS2 versus HAS1/HAS3 not tested
  19. 2022 High

    Alternative polyadenylation was identified as a disease-relevant regulator: NUDT21 depletion causes 3′ UTR shortening of HAS2 mRNA, leading to HAS2 hyper-expression and metabolic dysfunction in pulmonary artery SMCs; transgenic SM-specific HAS2 overexpression caused spontaneous pulmonary hypertension, while conditional Has2 deletion prevented experimental PH.

    Evidence NUDT21 knockdown, APA analysis, SM-HAS2 transgenic mice, Has2 conditional deletion, Seahorse metabolic analysis, pulmonary hemodynamics

    PMID:35671866

    Open questions at the time
    • Whether 3′ UTR shortening affects HAS2 mRNA stability, translation efficiency, or miRNA targeting not fully dissected
    • Human PH patient validation limited
  20. 2023 High

    Cross-species gain-of-function demonstrated that naked mole-rat HAS2, producing elevated HMM-HA, extends murine lifespan and healthspan while reducing cancer incidence and multi-tissue inflammation, establishing HAS2-produced HMM-HA as a systemic longevity and anti-inflammatory factor.

    Evidence nmrHas2 transgenic mice, lifespan/cancer incidence tracking, multi-tissue transcriptomics, immune cell assays, gut barrier permeability

    PMID:37612507

    Open questions at the time
    • Specific sequence differences in nmrHAS2 versus human HAS2 responsible for HMM-HA not defined
    • Whether benefits are solely from HA size or also from expression level/tissue distribution unclear
  21. 2025 High

    In the tumor microenvironment, CAF-derived HAS2 was shown to drive a bidirectional signaling loop: LMW-HA activates YAP in cancer cells, releasing CTGF that further stimulates CAF HAS2 expression; conditional Has2 deletion from hepatic stellate cells reduced liver metastasis, collagen/HA deposition, and immunosuppressive M2 macrophage infiltration.

    Evidence Conditional Has2 deletion in HSCs, MC38 metastasis model, scRNA-seq, YAP inhibition, anti-PD-1 combination in mice

    PMID:39946200

    Open questions at the time
    • Whether the YAP-CTGF-HAS2 loop operates in non-hepatic metastatic niches not tested
    • Direct binding of LMW-HA to a specific receptor activating YAP not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the three-dimensional structure of HAS2 and the mechanism by which ubiquitination activates catalysis are unknown; how HAS2 promotes EMT cell-autonomously (independent of extracellular HA) is unresolved; the relative contributions of intracellular HA, UDP-sugar depletion, and non-catalytic HAS2 scaffolding to its cell-autonomous functions have not been separated; and whether therapeutic targeting of the HAS2 PTM code or the CAF-tumor HA loop can be translated to clinical benefit remains untested.
  • No structural model of any HAS family member
  • Cell-autonomous EMT mechanism not molecularly defined
  • Therapeutic targeting strategies not validated in clinical settings

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0031012 extracellular matrix 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 1 R-HSA-9612973 Autophagy 1
Partners
AMPKATG9ACD44HAS1HAS3SMAD4STAT3
Complex memberships
HAS1-HAS2 heteromerHAS2-HAS2 homomerHAS2-HAS3 heteromer

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Overexpression of HAS2 in human HT1080 fibrosarcoma cells directly increases hyaluronan production, promotes anchorage-independent growth (colony formation in semisolid medium), and enhances tumorigenicity (accelerated tumor growth in nude mice), demonstrating that HAS2-driven HA synthesis per se promotes tumor cell proliferation. Stable transfection of HAS2, soft-agar colony formation assay, nude mouse xenograft model Cancer research High 10070975
2004 In zebrafish, Has2 is required upstream of Rac1 to stimulate lamellipodia formation and dorsal cell migration during gastrulation; epistasis with constitutively active and dominant-negative Rac1 places Has2-driven HA as an autocrine signal that activates Rac1 to promote cell migration rather than acting purely as a structural ECM component. Antisense morpholino knockdown, ectopic expression, epistasis with CA/DN Rac1 constructs, live imaging of lamellipodia Development (Cambridge, England) High 14729574
2011 AMPK directly phosphorylates Thr-110 of HAS2, inhibiting its enzymatic activity and reducing hyaluronan synthesis without affecting HAS1 or HAS3; pharmacological AMPK activation (AICAR, metformin) or genetic knockout confirmed that this phosphorylation reduces HA-dependent smooth muscle cell proliferation, migration, and immune cell recruitment. AMPK activator treatment, specific AMPK inhibitor, AMPK knockout cell lines, in vitro phosphorylation assay identifying Thr-110 as the site, HA ELISA The Journal of biological chemistry High 21228273
2010 Proinflammatory cytokines (IL-1β, TNFα, TNFβ) induce HAS2 mRNA expression via the NF-κB signaling pathway in human umbilical vein endothelial cells, leading to increased HA synthesis; siRNA knockdown of HAS2 abolished HA synthesis and abrogated monocyte adhesion, demonstrating HAS2 is the critical mediator. Cytokine treatment, NF-κB pathway inhibition, HAS2-specific siRNA knockdown, monocyte adhesion assay, HA ELISA The Journal of biological chemistry High 20522558
2014 HAS2 transcription is controlled by its natural antisense RNA HAS2-AS1 via an O-GlcNAcylation-dependent epigenetic mechanism: O-GlcNAcylation recruits NF-κB p65 to the HAS2-AS1 promoter, and HAS2-AS1 then acts in cis to alter chromatin structure (via O-GlcNAcylation and acetylation) at the HAS2 proximal promoter, thereby increasing HAS2 transcription. Glucosamine/PUGNAC treatment to induce O-GlcNAcylation, HAS2-AS1-specific siRNA, NF-κB p65 ChIP, promoter acetylation assays, chromatin accessibility analysis The Journal of biological chemistry High 25183006
2012 TGFβ upregulates HAS2 expression via kinase-active TGFβ type I receptor, Smad signaling, and p38 MAPK activation in mammary epithelial cells; HAS2 knockdown inhibited TGFβ-induced EMT (~50% reduction by morphology/ZO-1 markers, reduced Snail1/Zeb1/fibronectin) and completely abolished TGFβ-induced cell migration, whereas extracellular HA removal or CD44 blockade did not inhibit EMT. TGFβ treatment, HAS2-specific siRNA, Smad pathway inhibition, p38 MAPK inhibition, Streptomyces hyaluronidase treatment, CD44 blocking antibodies, real-time PCR for EMT markers Oncogene High 23108409
2011 HAS2 knockdown in bone-metastatic MDA-MB-231 cells completely suppressed invasion by inducing TIMP-1 and dephosphorylating focal adhesion kinase (FAK); HAS2 knockdown also suppressed EGF-mediated FAK/PI3K/Akt signaling; rescue with HAS2 overexpression, TIMP-1 siRNA, or TIMP-1-blocking antibodies restored invasion. HAS2 siRNA knockdown, basement membrane invasion assay, TIMP-1 siRNA, TIMP-1 blocking antibodies, Western blot for pFAK and Akt, HAS2 overexpression rescue The Journal of biological chemistry High 22016393
2011 miR-23 directly targets Has2 mRNA in the embryonic heart endocardium; miR-23 loss leads to Has2 upregulation, excess HA production, and excessive endocardial cushion cell differentiation in zebrafish; Has2 was validated as a direct miR-23 target using in silico screening combined with in vivo functional testing. miRNA screening, zebrafish dicer mutant analysis, miR-23 gain/loss of function, in vivo validation of Has2 as target, endocardial cushion formation assay Circulation research High 21778427
2009 Conditional inactivation of Has2 in mouse limb bud mesoderm (Prx1-Cre) causes severe skeletal shortening, digit patterning defects, disorganized growth plates with reduced aggrecan, impaired hypertrophic chondrocyte differentiation, failure of secondary ossification center formation, and defective synovial joint cavity formation, establishing HA synthesized by Has2 as essential for skeletal growth, chondrocyte maturation, and joint formation. Conditional knockout (Has2 floxed × Prx1-Cre), skeletal staining, histology, immunostaining for aggrecan and hypertrophy markers, in situ hybridization Development (Cambridge, England) High 19633173
2015 HAS1, HAS2, and HAS3 form homo- and heteromeric complexes with each other (HAS1-HAS2, HAS2-HAS2, HAS2-HAS3, and all other combinations) in both Golgi and plasma membrane; complexes were detected by FRET in live cells, proximity ligation assay with endogenous antibodies, and confirmed by acceptor photobleaching; complex formation is mediated primarily via the N-terminal 86-amino acid domain; HAS1 co-expression reduces HAS2- and HAS3-driven HA synthesis, indicating functional cooperation. FRET with flow cytometric quantification, FRET microscopy with acceptor photobleaching, proximity ligation assay, C-terminal deletion mutagenesis, HA synthesis assay The Journal of biological chemistry High 25795779
2018 Post-translational modifications control HAS2 trafficking and activity: (1) ubiquitination at K190 is required for HA synthesis (K190R blocks synthesis) and for PM residence; (2) phosphorylation at T110 is required for ER-to-PM trafficking (T110A remains in ER, absent from PM, and is enzymatically inactive); (3) O-GlcNAcylation at S221 stabilizes HAS2 (S221A reduces HA synthesis; phosphomimetic S221D/E destabilizes enzyme). K190R acts as dominant-negative for HA synthesis when co-transfected with WT HAS2. HAS2-stimulated extracellular vesicle shedding depends on PM residence but not HA synthesis. Site-directed mutagenesis of K190R, T110A, S221A/D/E; EGFP-HAS2 and Dendra2-HAS2 trafficking by confocal and TIRF microscopy; cell-surface biotinylation; photo-conversion pulse-chase; Rab10 siRNA; HA ELISA Matrix biology : journal of the International Society for Matrix Biology High 30394292
2002 Stable Has2 sense (overexpression) and antisense (knockdown) keratinocyte cell lines show that Has2-driven HA synthesis controls migration, lamellipodia extension, and cell spreading: Has2 antisense cells migrate more slowly, have smaller lamellipodia, delayed S-phase entry, and increased vinculin-positive adhesion plaques. Exogenous HA or hyaluronidase treatment could not fully replicate these effects, suggesting the dynamic synthesis process—not merely the presence of HA—regulates these functions. Stable transfection of Has2 sense/antisense constructs, in vitro wound assay, cell cycle analysis, lamellipodia measurement, vinculin staining, exogenous HA and Streptomyces hyaluronidase treatment Journal of cell science High 12186949
2004 Vasodilatory prostaglandins (prostacyclin analogue iloprost, EP2 agonist butaprost, PGE2) upregulate HAS2 mRNA and HA synthesis in human arterial smooth muscle cells via EP2 and IP receptors and cAMP signaling (mimicked by stable cAMP analogues and forskolin); HAS2-specific RNAi abolished iloprost-induced HA secretion and HAS2 knockdown increased cell spreading. RT-PCR, RNAi/siRNA targeting HAS2, cAMP analogues/forskolin, receptor-selective agonists, HA secretion assay, cell spreading assay Circulation research High 14752026
2011 The HAS2–HYAL2–CD44 system on the plasma membrane generates fragmented (low molecular weight) HA from HMW-HA as an autocrine chemokinetic signal: HAS2 knockdown reduced spontaneous chemokinesis of HeLa-S3 cells; HYAL2 or CD44 knockdown similarly reduced chemokinesis; exogenous LMW-HA rescued HYAL2 siRNA-mediated reduction in motility. siRNA knockdown of HAS2, HYAL2, CD44; spontaneous chemokinesis assay; HA size exclusion chromatography; exogenous LMW-HA rescue International journal of oncology Medium 21743962
2016 CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates that HA is essential for aggrecan retention in the pericellular matrix: Has2 KO cells cannot assemble a particle-excluding pericellular matrix and fail to retain exogenous aggrecan; adenoviral re-expression of HAS2 restored pericellular matrices and aggrecan incorporation. CRISPR/Cas9 Has2 knockout, pericellular matrix assay with particle exclusion, exogenous aggrecan addition, adenoviral HAS2 rescue, pellet culture neocartilage model Matrix biology : journal of the International Society for Matrix Biology High 27094859
2013 HAS1 requires approximately 10-fold higher cellular UDP-GlcNAc concentration than HAS2 and HAS3 to synthesize HA; HAS2 activity increases with UDP-sugar availability while HAS3 is active even at minimal substrate levels; transfected Has2 and Has3 consume sufficient UDP-sugars to measurably reduce their cellular content in COS-1 cells. Transfection of HAS1-3 into COS-1 cells, glucosamine supplementation to vary UDP-GlcNAc, glucose-free medium depletion, HPLC UDP-sugar quantification, HA ELISA The Journal of biological chemistry High 23303191
2011 SIRT1 activation reduces HAS2 expression and pericellular HA production in human aortic smooth muscle cells by preventing nuclear translocation of NF-κB p65, which in turn reduces HAS2-AS1 long noncoding RNA levels (which epigenetically control HAS2 mRNA expression); SIRT1 activation also reduces RHAMM and TSG6 expression, thereby inhibiting HA-mediated monocyte adhesion and cell migration. SIRT1 activators (SRT1720, resveratrol), NF-κB nuclear translocation assay, HAS2-AS1 quantification, monocyte adhesion assay, migration assay, pericellular HA coat measurement The Journal of biological chemistry High 31932306
2014 Extracellular UDP-glucose activates the P2Y14 receptor on keratinocytes, triggering JAK2 and ERK1/2 activation and specific Tyr705 phosphorylation of STAT3; phospho-STAT3 binds to the HAS2 promoter (confirmed by ChIP) to induce HAS2 transcription and subsequent hyaluronan synthesis, migration, and proliferation. UDP-glucose treatment, P2Y14 receptor identification (Gi inhibitor), JAK2/STAT3 inhibitors, ChIP demonstrating pY705-STAT3 binding to HAS2 promoter, HAS2 mRNA quantification, migration/proliferation assays The Journal of biological chemistry High 24847057
2018 TGFβ activates Smad and non-Smad (Akt, Erk1/2) pathways to induce Has2, Has2as (natural antisense), and Hmga2; Has2as is required for TGFβ-induced EMT (abrogation of Has2as suppressed Snai1, Hmga2, Fn1, and mesenchymal phenotype); Has2as maintains breast cancer stemness; CD44 (but not Hmmr) is required for TGFβ-mediated EMT phenotype. siRNA knockdown of Has2as/Hmga2, TGFβ treatment, EMT marker qPCR, Akt/Erk1/2 inhibition, CD44/Hmmr siRNA, stemness marker analysis, migration assay Matrix biology : journal of the International Society for Matrix Biology High 30194979
2009 Has2 mRNA knockdown in mouse cumulus cell-oocyte complexes via adenovirus-mediated shRNA (>70% suppression) significantly reduces cumulus expansion in response to EGF stimulation, demonstrating that Has2 expression in cumulus cells is required for this developmental process; Has2 shRNA also reduced Areg and Ereg mRNA levels but not Ptgs2, Ptx3, or Tnfaip6. Adenovirus-mediated shRNA delivery to intact COCs, EGF-stimulated cumulus expansion assay, qRT-PCR for Has2 and expansion-related transcripts Molecular reproduction and development Medium 18951380
2020 HAS2 protein in vascular endothelial cells is degraded via autophagy: nutrient deprivation, mTOR inhibition, or pro-autophagic proteoglycan fragments (endorepellin/endostatin) induce autophagy and HAS2 degradation; super-resolution microscopy revealed dynamic interaction between HAS2 and the autophagic transmembrane protein ATG9A; chloroquine (autophagy flux inhibitor) increased HAS2 levels in vivo; autophagic induction suppressed HA production and angiogenic sprouting ex vivo. Live-cell and super-resolution confocal microscopy, co-localization of HAS2 with ATG9A, mTOR inhibition, chloroquine treatment in vivo (heart and aorta), ex vivo angiogenic sprouting assay, HA ELISA Matrix biology : journal of the International Society for Matrix Biology High 32084457
2018 Extracellular ATP activates HAS2 expression in human keratinocytes via the purinergic P2Y2 receptor through protein kinase C, CaMKII, MAPK, and CREB-dependent pathways; UDP-glucose activates HAS2 via P2Y14-JAK2-STAT3 signaling; AMP and adenosine (ATP degradation products) markedly inhibit HAS2 expression, providing a feedback mechanism to shut off the hyaluronan response. ATP/AMP/adenosine treatments, P2Y2 receptor identification (Gi inhibitor), PKC/CaMKII/MAPK/CREB inhibitors, HAS2 mRNA quantification, pericellular HA accumulation assay, migration assay The Biochemical journal Medium 29626161
2019 HAS2 overexpression in chondrocytes inhibits the procatabolic phenotype (reduces MMP3, MMP13, TSG6, IL-1β-induced markers) and enhances aggrecan retention through a cell-autonomous mechanism independent of extracellular HA: neighboring non-transduced chondrocytes were not protected by the excess HA produced by transduced cells, and HAS2-OE shifted chondrocyte metabolism from glycolysis toward oxidative phosphorylation. Inducible adenoviral HAS2 overexpression, co-culture of transduced and non-transduced chondrocytes, MMP/aggrecan Western blot/ELISA, Seahorse metabolic flux analysis The Journal of biological chemistry High 31270213
2023 KIAA1429/VIRMA, when mislocalized to the cytosol of breast cancer cells, binds to the m6A RNA-binding protein IGF2BP3, which recruits and stabilizes m6A-modified HAS2 mRNA; KIAA1429/VIRMA knockdown inhibits breast cancer proliferation, migration, and invasion, with HAS2 mRNA levels positively correlating with KIAA1429/VIRMA in breast cancer tissue. shRNA knockdown, co-immunoprecipitation of VIRMA-IGF2BP3, m6A modification detection, HAS2 mRNA stability assay, proliferation/migration/invasion assays EMBO reports Medium 37705505
2022 3' UTR shortening of HAS2 mRNA caused by depletion of NUDT21 (a master regulator of alternative polyadenylation) in pulmonary artery smooth muscle cells leads to HAS2 hyper-expression and HA hyper-synthesis; this promotes bioenergetic dysfunction (impaired mitochondrial oxidative capacity, glycolytic shift), cell proliferation/migration/apoptosis-resistance, and pulmonary artery contractility. Transgenic smooth muscle-specific HAS2 overexpression mice developed spontaneous pulmonary hypertension; targeted HAS2 deletion prevented experimental PH. NUDT21 knockdown, alternative polyadenylation analysis, transgenic mice (SM-HAS2), Has2 conditional deletion, Seahorse metabolic flux analysis, pulmonary hemodynamics measurement Matrix biology : journal of the International Society for Matrix Biology High 35671866
2007 LIF induces HAS2 expression (identified by differential display screening) and HA production in fetal rat calvaria osteoprogenitor cells; exogenous high-molecular-weight HA dose-dependently inhibited osteoblast differentiation at the same stage as LIF; hyaluronidase treatment stimulated bone nodule formation at early stages, establishing HAS2/HA as a mediator of LIF-induced arrest of osteoblast differentiation. Differential display screening, HA ELISA, exogenous HMW-HA treatment, hyaluronidase treatment, bone nodule formation assay, stage-specific pulse treatment Journal of bone and mineral research Medium 17451373
2011 In zebrafish, Nephronectin (Npnt) knockdown prevents cardiac valve formation; the earliest endocardial phenotype involves ectopic has2 expression; inhibition of has2 in npnt morphants rescues the endocardial expansion but not myocardial expansion, whereas BMP signaling reduction rescues both; this places Npnt upstream of a Bmp4-Has2 signaling axis in AV canal differentiation. Morpholino knockdown of Npnt and has2, BMP signaling inhibition, in situ hybridization for has2/notch1b/bmp4/tbx2b, genetic epistasis in double morphants Development (Cambridge, England) High 21937601
2016 Med10 regulates heart valve formation in zebrafish by mediating Tbx2b expression, which in turn controls has2 transcription and cardiac jelly HA production; has2 is completely absent in med10 (ping pong) mutant hearts; reconstitution of Tbx2b expression rescues AV canal development in med10 mutants, and Foxn4 overexpression cannot rescue tbx2b expression, placing Med10 upstream of Foxn4-Tbx2b-Has2 in valve development. Insertional promoter mutant characterization, Tbx2b rescue by transient expression, Foxn4 overexpression epistasis, in situ hybridization for has2 Biochemical and biophysical research communications Medium 27343557
2019 HA oligosaccharides stimulate HAS2 expression in chondrocytes via the PI3K/Akt pathway (blocked by wortmannin/LY294002), distinct from the p38/NF-κB pathway used for MMP-3 induction; Akt phosphorylation mediates HAS2 promoter activation (confirmed by luciferase reporter assay); these are separate parallel signaling branches from CD44 engagement. HA oligosaccharide treatment, PI3K inhibitors (wortmannin, LY294002), p38/NF-κB inhibitors, Western blot for Akt phosphorylation, HAS2 proximal promoter luciferase reporter, HAS2 mRNA RT-PCR Osteoarthritis and cartilage Medium 19874928
2017 ZEB1 directly activates HAS2 expression in breast cancer cells, and HAS2-derived HA elevates ZEB1 expression in cooperation with CD44s (short isoform of CD44), forming a positive feedback loop; this ZEB1/HAS2/HA autocrine loop promotes EMT and osteoclast-stimulating activity indicative of bone metastasis potential. Correlation analysis across cancer datasets, HA-conditioned medium treatment, siRNA knockdown, ChIP for ZEB1 binding to HAS2 promoter, osteoclast formation assay, EMT marker analysis Oncotarget Medium 28086235
2023 Transgenic mice expressing naked mole-rat HAS2 (nmrHas2) show increased high-molecular-mass hyaluronan in multiple tissues, reduced spontaneous and induced cancer incidence, extended lifespan, improved healthspan, and attenuated multi-tissue inflammation; transcriptome analysis showed shift toward longer-lived species signatures; HMM-HA reduced inflammation via direct immunoregulatory effects on immune cells, protection from oxidative stress, and improved gut barrier function. Transgenic mouse generation (nmrHas2), cancer incidence measurement, lifespan analysis, multi-tissue transcriptomics, immune cell functional assays, HA size analysis, gut barrier permeability assay Nature High 37612507
2014 Spatially restricted Has2 expression and HA production at the tips of growing tubules drives epithelial tubulogenesis; silencing Has2 or inhibiting HA synthesis (4-MU) abrogates tube formation induced by TGFβ1 or HGF; knockdown of CD44 or RHAMM did not alter tubulogenesis, indicating the process is not HA receptor-mediated but depends on HA production itself. Has2 mRNA silencing, 4-MU HA synthesis inhibition, immunostaining for HA in tubules, CD44/RHAMM siRNA, ERK and S6 phosphorylation analysis, 3D tubulogenesis assay American journal of physiology. Cell physiology Medium 25163516
2012 Melanoma cell-derived factors upregulate Has2 expression (~20-fold) in dermal fibroblasts via PDGFR-PI3K-AKT and p38 signaling; Has2 knockdown abolished melanoma CM-induced HA synthesis increase and reversed fibroblast invasion into collagen matrix; PDGFR siRNA also blocked Has2 upregulation, identifying PDGF as the key melanoma-derived factor. Conditioned medium treatment, phosphokinase array, specific kinase inhibitors (PI3K, AKT, p38, PDGFR), Has2 siRNA, PDGFRα/β siRNA, collagen invasion assay Histochemistry and cell biology Medium 22825838
2019 SMAD4 directly binds to the HAS2 promoter (ChIP confirmation) to activate HAS2 transcription as part of TGFβ/SMAD4 signaling in porcine granulosa cells, driving HA synthesis and regulating granulosa cell proliferation and apoptosis via the downstream CD44-Caspase3 axis; miR-26b attenuates HAS2 expression via SMAD4-dependent and -independent mechanisms. SMAD4 overexpression/knockdown, ChIP demonstrating SMAD4 binding to HAS2 promoter, HAS2 promoter luciferase reporter, HA ELISA, CD44/Caspase3 western blot, miR-26b manipulation Journal of cellular physiology High 31489963
2025 Has2 deletion from hepatic stellate cells (Has2ΔHSC mice) reduces steatotic liver-associated metastatic tumor growth, collagen and HA deposition, and CAF/M2 macrophage infiltration; low-molecular-weight HA activates YAP in cancer cells, which releases CTGF to further activate CAFs for HAS2 expression, creating a bidirectional CAF-tumor loop; single-cell analyses link CAF-derived HAS2 to M2 macrophages and CRC cells through CD44. Conditional Has2 knockout (Has2ΔHSC), metastasis model (MC38 CRC cells in high-fat diet mice), single-cell RNA sequencing, YAP inhibition, HA synthesis inhibitors, anti-PD-1 antibody combination, collagen/HA staining The Journal of clinical investigation High 39946200

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Overproduction of hyaluronan by expression of the hyaluronan synthase Has2 enhances anchorage-independent growth and tumorigenicity. Cancer research 244 10070975
2005 The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer. Experimental cell research 186 16125700
2003 EGF upregulates, whereas TGF-beta downregulates, the hyaluronan synthases Has2 and Has3 in organotypic keratinocyte cultures: correlations with epidermal proliferation and differentiation. The Journal of investigative dermatology 139 12787132
2012 Efficient TGFβ-induced epithelial-mesenchymal transition depends on hyaluronan synthase HAS2. Oncogene 127 23108409
2004 Has2 is required upstream of Rac1 to govern dorsal migration of lateral cells during zebrafish gastrulation. Development (Cambridge, England) 120 14729574
2009 Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. Development (Cambridge, England) 119 19633173
2014 Natural antisense transcript for hyaluronan synthase 2 (HAS2-AS1) induces transcription of HAS2 via protein O-GlcNAcylation. The Journal of biological chemistry 109 25183006
2010 Proinflammatory cytokines induce hyaluronan synthesis and monocyte adhesion in human endothelial cells through hyaluronan synthase 2 (HAS2) and the nuclear factor-kappaB (NF-kappaB) pathway. The Journal of biological chemistry 108 20522558
2011 A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs. PLoS genetics 107 21437276
2011 Hyaluronan synthesis is inhibited by adenosine monophosphate-activated protein kinase through the regulation of HAS2 activity in human aortic smooth muscle cells. The Journal of biological chemistry 101 21228273
2011 MicroRNA-23 restricts cardiac valve formation by inhibiting Has2 and extracellular hyaluronic acid production. Circulation research 100 21778427
2011 Hyaluronan synthase 2 (HAS2) promotes breast cancer cell invasion by suppression of tissue metalloproteinase inhibitor 1 (TIMP-1). The Journal of biological chemistry 98 22016393
2013 Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS3. The Journal of biological chemistry 96 23303191
2023 Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice. Nature 83 37612507
2011 The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell. The Journal of biological chemistry 82 21357421
2017 Long noncoding RNA HAS2-AS1 mediates hypoxia-induced invasiveness of oral squamous cell carcinoma. Molecular carcinogenesis 76 28485478
2018 Tumor-suppressive functions of 4-MU on breast cancer cells of different ER status: Regulation of hyaluronan/HAS2/CD44 and specific matrix effectors. Matrix biology : journal of the International Society for Matrix Biology 69 29673760
2004 Induction of hyaluronic acid synthase 2 (HAS2) in human vascular smooth muscle cells by vasodilatory prostaglandins. Circulation research 68 14752026
2018 Interconnected feedback loops among ESRP1, HAS2, and CD44 regulate epithelial-mesenchymal plasticity in cancer. APL bioengineering 65 31069317
2017 A novel ZEB1/HAS2 positive feedback loop promotes EMT in breast cancer. Oncotarget 62 28086235
2012 Hyaluronic acid, HAS1, and HAS2 are significantly upregulated during muscle hypertrophy. American journal of physiology. Cell physiology 62 22785117
2020 Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis. Cancer gene therapy 60 32862195
2002 Changed lamellipodial extension, adhesion plaques and migration in epidermal keratinocytes containing constitutively expressed sense and antisense hyaluronan synthase 2 (Has2) genes. Journal of cell science 57 12186949
2014 HAS2 and CD44 in breast tumorigenesis. Advances in cancer research 56 25081531
2009 Targeted suppression of Has2 mRNA in mouse cumulus cell-oocyte complexes by adenovirus-mediated short-hairpin RNA expression. Molecular reproduction and development 55 18951380
2007 Putative role of hyaluronan and its related genes, HAS2 and RHAMM, in human early preimplantation embryogenesis and embryonic stem cell characterization. Stem cells (Dayton, Ohio) 55 17872502
2011 Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish. Development (Cambridge, England) 52 21937601
2016 Conserved miR-26b enhances ovarian granulosa cell apoptosis through HAS2-HA-CD44-Caspase-3 pathway by targeting HAS2. Scientific reports 51 26887530
2014 Extensive CD44-dependent hyaluronan coats on human bone marrow-derived mesenchymal stem cells produced by hyaluronan synthases HAS1, HAS2 and HAS3. The international journal of biochemistry & cell biology 49 24406795
2018 Has2 natural antisense RNA and Hmga2 promote Has2 expression during TGFβ-induced EMT in breast cancer. Matrix biology : journal of the International Society for Matrix Biology 45 30194979
2020 Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2-AS1. The Journal of biological chemistry 44 31932306
2014 Extracellular UDP-glucose activates P2Y14 Receptor and Induces Signal Transducer and Activator of Transcription 3 (STAT3) Tyr705 phosphorylation and binding to hyaluronan synthase 2 (HAS2) promoter, stimulating hyaluronan synthesis of keratinocytes. The Journal of biological chemistry 42 24847057
2019 CREB1 induced lncRNA HAS2-AS1 promotes epithelial ovarian cancer proliferation and invasion via the miR-466/RUNX2 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 40 31082772
2019 HAS2-AS1 is a novel LH/hCG target gene regulating HAS2 expression and enhancing cumulus cells migration. Journal of ovarian research 38 30819231
2018 Effects of mutations in the post-translational modification sites on the trafficking of hyaluronan synthase 2 (HAS2). Matrix biology : journal of the International Society for Matrix Biology 37 30394292
2015 Fluorescence resonance energy transfer (FRET) and proximity ligation assays reveal functionally relevant homo- and heteromeric complexes among hyaluronan synthases HAS1, HAS2, and HAS3. The Journal of biological chemistry 36 25795779
2014 The ABA-deficiency suppressor locus HAS2 encodes the PPR protein LOI1/MEF11 involved in mitochondrial RNA editing. Molecular plant 35 25708384
2018 Extracellular ATP activates hyaluronan synthase 2 (HAS2) in epidermal keratinocytes via P2Y2, Ca2+ signaling, and MAPK pathways. The Biochemical journal 32 29626161
2020 The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1. Bioscience reports 31 32776110
2016 CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention. Matrix biology : journal of the International Society for Matrix Biology 31 27094859
2004 Light and metabolic regulation of HAS1, HAS1.1 and HAS2, three asparagine synthetase genes in Helianthus annuus. Plant physiology and biochemistry : PPB 30 15246064
2016 GREM1, EGFR, and HAS2; the oocyte competence markers for improved buffalo embryo production in vitro. Theriogenology 29 27448692
2010 Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos. Birth defects research. Part A, Clinical and molecular teratology 28 20306498
2020 Autophagic degradation of HAS2 in endothelial cells: A novel mechanism to regulate angiogenesis. Matrix biology : journal of the International Society for Matrix Biology 27 32084457
2019 Long noncoding RNA HAS2-AS1 promotes tumor progression in glioblastoma via functioning as a competing endogenous RNA. Journal of cellular biochemistry 26 31385362
2007 LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 17451373
2023 KIAA1429/VIRMA promotes breast cancer progression by m6 A-dependent cytosolic HAS2 stabilization. EMBO reports 23 37705505
2016 The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation. Biochemical and biophysical research communications 22 27343557
2014 Genomewide association study identifies HAS2 as a novel susceptibility gene for adult asthma in a Japanese population. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 22 25251750
2012 Melanoma cell-derived factors stimulate hyaluronan synthesis in dermal fibroblasts by upregulating HAS2 through PDGFR-PI3K-AKT and p38 signaling. Histochemistry and cell biology 22 22825838
2015 Undifferentiated myxoid lipoblastoma with PLAG1-HAS2 fusion in an infant; morphologically mimicking primitive myxoid mesenchymal tumor of infancy (PMMTI)--diagnostic importance of cytogenetic and molecular testing and literature review. Cancer genetics 21 26701195
2006 Has2 expression in heart forming regions is independent of BMP signaling. Gene expression patterns : GEP 21 16458617
2019 Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan. The Journal of biological chemistry 20 31270213
2011 Increased HAS2-driven hyaluronic acid synthesis in shar-pei dogs with hereditary cutaneous hyaluronosis (mucinosis). Veterinary dermatology 20 21718367
2011 Fragmented hyaluronan is an autocrine chemokinetic motility factor supported by the HAS2-HYAL2/CD44 system on the plasma membrane. International journal of oncology 20 21743962
2023 Human TMEM2 is not a catalytic hyaluronidase, but a regulator of hyaluronan metabolism via HYBID (KIAA1199/CEMIP) and HAS2 expression. The Journal of biological chemistry 19 37196767
2009 Hyaluronan oligosaccharide treatment of chondrocytes stimulates expression of both HAS-2 and MMP-3, but by different signaling pathways. Osteoarthritis and cartilage 18 19874928
2019 TGF-β/SMAD4 signaling pathway activates the HAS2-HA system to regulate granulosa cell state. Journal of cellular physiology 17 31489963
2021 LncRNA HAS2-AS1 Promotes Glioblastoma Proliferation by Sponging miR-137. Frontiers in oncology 16 34094916
2019 Silencing of HAS2-AS1 mediates PI3K/AKT signaling pathway to inhibit cell proliferation, migration, and invasion in glioma. Journal of cellular biochemistry 16 30790335
2022 The natural antisense transcript HAS2-AS1 regulates breast cancer cells aggressiveness independently from hyaluronan metabolism. Matrix biology : journal of the International Society for Matrix Biology 14 35395387
2021 The Transcription Factor C/EBPβ Promotes HFL-1 Cell Migration, Proliferation, and Inflammation by Activating lncRNA HAS2-AS1 in Hypoxia. Frontiers in cell and developmental biology 14 33777961
2020 Vitamin D regulation of HAS2, hyaluronan synthesis and metabolism in triple negative breast cancer cells. The Journal of steroid biochemistry and molecular biology 14 32360595
2020 Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway. American journal of translational research 13 32269726
2021 The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades. International journal of molecular sciences 12 33669634
2021 GNA14 stimulation of KLF7 promotes malignant growth of endometrial cancer through upregulation of HAS2. BMC cancer 12 33892667
2017 Evaluating The Effect of Melatonin on HAS2, and PGR expression, as well as Cumulus Expansion, and Fertility Potential in Mice. Cell journal 12 29308626
2023 Downregulation of HAS‑2 regulates the chondrocyte cytoskeleton and induces cartilage degeneration by activating the RhoA/ROCK signaling pathway. International journal of molecular medicine 11 37232339
2022 FGF9 Promotes Expression of HAS2 in Palatal Elevation via the Wnt/β-Catenin/TCF7L2 Pathway. Biomolecules 11 36358989
2021 WNT5A Enhances LH-Mediated Expression of HAS2 in Granulosa Cells. Reproductive sciences (Thousand Oaks, Calif.) 11 34542891
2020 Inhibition of HAS2 and hyaluronic acid production by 1,25-Dihydroxyvitamin D3 in breast cancer. Oncotarget 11 32774770
2019 Atherosclerosis-associated endothelial cell apoptosis by miRNA let7-b-mediated downregulation of HAS-2. Journal of cellular biochemistry 11 31736114
2018 Activin/Smad2 and Wnt/β-catenin up-regulate HAS2 and ALDH3A2 to facilitate mesendoderm differentiation of human embryonic stem cells. The Journal of biological chemistry 11 30282636
2013 Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage. Biochemical and biophysical research communications 11 24333416
2025 Metastatic tumor growth in steatotic liver is promoted by HAS2-mediated fibrotic tumor microenvironment. The Journal of clinical investigation 10 39946200
2024 Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti-Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus. Small (Weinheim an der Bergstrasse, Germany) 10 38593309
2022 3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension. Matrix biology : journal of the International Society for Matrix Biology 9 35671866
2022 Cell-Type-Specific Expression of Hyaluronan Synthases HAS2 and HAS3 Promotes Goblet Cell Hyperplasia in Allergic Airway Inflammation. American journal of respiratory cell and molecular biology 8 35679095
2022 The Upregulation of HAS2-AS1 Relates to the Granulosa Cell Dysfunction by Repressing TGF-β Signaling and Upregulating HAS2. Molecular and cellular biology 8 35938797
2021 Hyaluronan synthase 2 (HAS2) regulates cell phenotype and invadopodia formation in luminal-like breast cancer cells. Molecular and cellular biochemistry 8 33954907
2016 In Vitro Effects of HAS-2 Gene Silencing on the Proliferation and Apoptosis of the MCF-7 Human Breast Cancer Cell Line. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 8 27915342
2014 Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro. American journal of physiology. Cell physiology 8 25163516
2013 Triiodothyronine (T3) inhibits hyaluronate synthesis in a human dermal equivalent by downregulation of HAS2. In vitro cellular & developmental biology. Animal 8 23397370
2022 MicroRNA-101 regulates oocyte maturation in vitro via targeting HAS2 in porcine cumulus cells. Theriogenology 7 35567989
2017 Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease. American journal of respiratory cell and molecular biology 7 28787175
2024 Calycosin inhibits the proliferation and metastasis of renal cell carcinoma through the MAZ/HAS2 signaling pathway. Phytotherapy research : PTR 6 39120474
2022 HAS2-Ezrin-ER axis plays a role in acquired antiestrogen resistance of ER-positive breast cancer. Frontiers in pharmacology 6 36386154
2020 HAS2-AS1 Acts as a Molecular Sponge for miR-137 and Promotes the Invasion and Migration of Glioma Cells by Targeting EZH2. Cell cycle (Georgetown, Tex.) 6 33064966
2016 Impact of Prunus Cerasus on PGR and HAS2 in Cumulus Cells and Fertility Outcome. Advanced pharmaceutical bulletin 6 27123419
2023 MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2. Endocrine 5 37231239
2022 Has2 Regulates the Development of Ovalbumin-Induced Airway Remodeling and Steroid Insensitivity in Mice. Frontiers in immunology 5 35069543
2017 Effect of MT3 on Retinal and Choroidal TGF-β2 and HAS2 Expressions in Form Deprivation Myopia of Guinea Pig. Journal of ophthalmology 5 29163988
2024 Upregulation of HAS2 promotes glioma cell proliferation and chemoresistance via c-myc. Cellular signalling 4 38734194
2024 HAS2 facilitates glioma cell malignancy and suppresses ferroptosis in an FZD7-dependent manner. Cancer science 4 38816349
2012 Genetic association and gene-gene interaction of HAS2, HABP1 and HYAL3 implicate hyaluronan metabolic genes in glaucomatous neurodegeneration. Disease markers 4 22960332
2010 Over-expression of has2 in synovium-derived mesenchymal stem cells may prevent adhesions following surgery of the digital flexor tendons. Medical hypotheses 4 21084166
2024 Piceatannol enhances hyaluronic acid synthesis through SIRT1-Mediated HAS2 upregulation in human dermal fibroblasts. Biochemistry and biophysics reports 3 38910870
2024 Tanshinone IIA Protects Ischemia/Reperfusion-Induced Cardiomyocyte Injury by Inhibiting the HAS2/FGF9 Axis. Cardiology research and practice 2 39568660
2019 Expression of PTX3, HAS2 AND TNFAIP6 genes in relation to real-time proliferation of porcine endometrial luminal epithelial cells in primary cultivation model. Journal of biological regulators and homeostatic agents 2 31189490
2013 Marginal association between SNP rs2046571 of the HAS2 gene and Parkinson's disease in the Chinese female population. Neuroscience letters 2 23916661