Affinage

HMGA2

High mobility group protein HMGI-C · UniProt P52926

Length
109 aa
Mass
11.8 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HMGA2 is an intrinsically disordered, non-histone architectural chromatin protein with three consecutive AT-hook domains that bind the minor groove of AT-rich DNA and induce DNA bending, plus an acidic C-terminal domain encoded by a five-exon gene whose intron-3 breakpoint hotspot separates the two functional modules in mesenchymal tumors (PMID:8824803, PMID:8918814, PMID:32466162). As a transcriptional co-regulator it binds promoters directly and partners with sequence-specific factors: it occupies the SNAIL1 promoter and physically associates with TGF-β/Smad proteins to drive epithelial-mesenchymal transition (PMID:18832382), cooperates with C/EBPβ to recruit it to the Pparγ2 promoter during adipogenesis (PMID:26966068), and binds the Twist1, Atg10, and GPX4 promoters to control vasculogenic mimicry, autophagy, and ferroptosis resistance respectively (PMID:28533522, PMID:28510366, PMID:38493165). Through these and additional outputs—TGF-β type II receptor induction, suppression of TET1 and the HOXA epigenetic program, PI3K/AKT/mTOR and IGF2BP2/pAKT signaling, and E2F1 derepression via HDAC1 displacement from the pRB complex—HMGA2 promotes invasion, proliferation, and stem-cell self-renewal across multiple tumor types (PMID:23722545, PMID:23716660, PMID:16969098, PMID:26319392, PMID:32868105, PMID:27259253). It also acts post-transcriptionally on p53, forming a complex with p53 and MDM2 via its AT-hook domains to promote MDM2-mediated p53 degradation (PMID:30175854). Independently of its transcriptional roles, HMGA2 functions as a replication fork chaperone that preferentially binds supercoiled DNA plectonemes and stabilizes them against topoisomerase relaxation, protecting stalled forks from endonucleolytic collapse (PMID:24508460, PMID:28814752). Physiologically HMGA2 is required for adipogenesis, neural crest and retinal progenitor self-renewal, and chondrocyte protection within the Lin28-Let7 axis (PMID:10742101, PMID:26806704, PMID:25336737, PMID:36026443). HMGA2 haploinsufficiency from an intronic splicing mutation causes a Silver-Russell-syndrome-like growth phenotype in humans (PMID:25809938).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Establishing the gene/protein architecture defined HMGA2 as a modular AT-hook DNA-binding protein and located the mesenchymal-tumor breakpoint hotspot.

    Evidence Genomic cloning, Southern/Northern blotting, and protein structural analysis defining five exons, three AT-hooks, an acidic domain, and the intron-3 breakpoint

    PMID:8824803 PMID:8918814

    Open questions at the time
    • Did not establish DNA sequence specificity or in vivo binding sites
    • Function of the separated acidic domain in disease left mechanistically open
  2. 1999 Medium

    Identifying HMGA2 as a growth-factor-induced delayed-early gene placed its expression downstream of mitogenic signaling.

    Evidence Promoter-reporter assays and PI-3K/MAPK inhibitor experiments with FGF-1/PDGF-BB stimulation in 3T3-L1 preadipocytes

    PMID:10490844

    Open questions at the time
    • Did not identify the transcription factors mediating induction
    • No connection to a specific downstream HMGA2 function
  3. 2000 High

    Knockout genetics established that HMGA2 is physiologically required for adipogenesis, moving it from a tumor marker to a developmental regulator.

    Evidence Hmgic-/- and transgenic mice with gene-dose-dependent fat-mass phenotypes in diet-induced and ob/ob obesity models

    PMID:10742101

    Open questions at the time
    • Molecular mechanism of adipogenic requirement not defined
    • Target genes in fat cells unidentified at this stage
  4. 2006 Medium

    An epistasis cross showed HMGA2 drives proliferation by activating E2F1, revealing a chromatin-remodeling route to cell-cycle derepression.

    Evidence HMGA2 transgenic × E2F1-knockout mouse genetics with molecular characterization of E2F1 acetylation and HDAC1 displacement from pRB/E2F1

    PMID:16969098

    Open questions at the time
    • Direct enzymatic mechanism of E2F1 acetylation by HMGA2 not resolved
    • Generalizability beyond pituitary adenoma untested here
  5. 2008 High

    Direct promoter binding plus Smad interaction established HMGA2 as a transcriptional driver of the EMT program via SNAIL1.

    Evidence ChIP, Co-IP, promoter-reporter assays, and SNAIL1 knockdown rescue in epithelial cells

    PMID:18832382

    Open questions at the time
    • Whether HMGA2 acts as classic activator or architectural facilitator not distinguished
    • Other EMT targets not mapped
  6. 2013 High

    Multiple studies built out the metastasis network downstream of HMGA2, including TGF-βRII upregulation, TET1/HOXA epigenetic suppression, and miR-200b/LOX and SDC2 control.

    Evidence Mouse allograft/xenograft and MMTV-Wnt models, ChIP, bisulfite sequencing, and expression analyses

    PMID:23716660 PMID:23722545 PMID:23975428

    Open questions at the time
    • Direct versus indirect promoter occupancy not resolved for every target
    • Relative contribution of each branch to metastasis unquantified
  7. 2014 High

    HMGA2 was assigned a non-transcriptional role as a replication fork chaperone, protecting stalled forks from collapse via its AT-hook domains.

    Evidence In vitro DNA-binding/domain-mapping assays and DNA strand-break measurement in ESC and cancer heterologous cell systems

    PMID:24508460

    Open questions at the time
    • Precise branched-DNA scaffold geometry not solved structurally
    • Interplay with canonical fork-protection factors not defined
  8. 2014 Medium

    Functional studies extended HMGA2 to stem/progenitor self-renewal and identified PLAG1 as a downstream activated gene.

    Evidence Clonal RPC self-renewal assays in vitro/in vivo and HMGA2 overexpression inducing PLAG1 in MCF-7 and ADSCs

    PMID:24516594 PMID:25336737

    Open questions at the time
    • Direct PLAG1 promoter binding not demonstrated
    • Cell-extrinsic signal mediating RPC self-renewal not molecularly identified
  9. 2015 Medium

    Human and mouse genetics linked HMGA2 loss-of-function to growth deficiency and confirmed AML proliferation via PI3K/Akt/mTOR.

    Evidence Intronic splicing mutation/splicing assay in Silver-Russell syndrome family; HMGA2 knockdown reducing pAkt/pmTOR in AML with xenograft

    PMID:25809938 PMID:26319392

    Open questions at the time
    • Mechanism connecting HMGA2 dosage to growth phenotype unresolved
    • Whether AKT/mTOR effect is transcriptional or indirect not established
  10. 2016 Medium

    HMGA2 was shown to recruit C/EBPβ to the Pparγ2 promoter and to act within neural crest and glioma stem-cell networks, generalizing its co-factor and self-renewal roles.

    Evidence ChIP/Co-IP/reporter assays in 3T3-L1; Xenopus morpholino epistasis; shRNA knockdown in glioma-initiating cells with FOXM1/PLAU readout

    PMID:26806704 PMID:26966068 PMID:27259253

    Open questions at the time
    • Whether co-factor recruitment is direct chromatin remodeling or stabilization unclear
    • Direct promoter binding for FOXM1/PLAU not shown
  11. 2017 High

    Biochemistry defined HMGA2's preference for supercoiled plectonemes and its topoisomerase-modulating activity, mechanistically explaining fork protection and chemotherapy responses; promoter studies added Twist1 and Atg10 targets.

    Evidence In vitro DNA-structure binding and topoisomerase relaxation assays; ChIP/reporter assays for Twist1 (VE-cadherin) and Atg10 (autophagy)

    PMID:28510366 PMID:28533522 PMID:28814752

    Open questions at the time
    • Stoichiometry of supercoil constraining in vivo not measured
    • Direct vs cooperative occupancy of Twist1/Atg10 promoters not fully dissected
  12. 2018 High

    Domain-mapped interactions established a post-transcriptional oncogenic axis in which HMGA2 promotes MDM2-mediated p53 degradation.

    Evidence Co-IP with deletion mutants, ubiquitination assays, and Hmga2 knock-in carcinogen-induced tumor mouse model

    PMID:30175854

    Open questions at the time
    • Whether this competes with HMGA2's chromatin functions unknown
    • Structural basis of the ternary HMGA2-p53-MDM2 complex unsolved
  13. 2019 Medium

    The supercoil-constraining model was translated to drug response, showing HMGA2 dose-dependently modulates TOP1-poison-induced DNA breaks.

    Evidence Cell-based, in vitro ternary-complex, and patient-derived xenograft assays with DNA break quantification

    PMID:31067275

    Open questions at the time
    • Threshold separating protective vs sensitizing HMGA2 levels not defined clinically
    • Subtelomeric vulnerability mechanism incompletely characterized
  14. 2020 Medium

    Biophysical characterization confirmed HMGA2 as an intrinsically disordered, homodimerizing DNA-bender and identified suramin as an AT-hook-targeting inhibitor; GPX4 was added as a transcriptional/translational target controlling ferroptosis; and an HMGA2/IGF2BP2 angiogenic axis was defined.

    Evidence IDP/dimerization/DNA-binding assays, AlphaScreen inhibitor screen, ChIP with histone marks and mTORC1 interrogation for GPX4, and HUVEC/xenograft assays with IGF2BP2 silencing

    PMID:32466162 PMID:32868105 PMID:33139812 PMID:38493165

    Open questions at the time
    • Suramin binding mode lacks mutagenesis confirmation
    • How a disordered protein achieves promoter selectivity remains unresolved
  15. 2022 High

    Conditional mouse genetics placed HMGA2 as an essential SOX9-activating mediator within the Lin28a-Let7 axis protecting cartilage.

    Evidence Cartilage-specific conditional knockout/overexpression, RNA-seq, siRNA rescue, and osteoarthritis mouse model

    PMID:36026443

    Open questions at the time
    • Direct SOX9 promoter binding not demonstrated
    • Whether cartilage role uses chromatin or fork functions undetermined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How an intrinsically disordered protein with only AT-hook minor-groove binding achieves gene- and locus-specific selectivity across its many transcriptional, replicative, and protein-degradation activities remains unresolved.
  • No structural model of HMGA2 on a specific target promoter
  • Unclear what dictates the choice between architectural transcription, fork chaperoning, and p53 regulation in a given cell

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 4 GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-69306 DNA Replication 2
Partners
CEBPBIGF2BP2MDM2SMADTP53

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 HMGA2 directly binds to the SNAIL1 promoter and acts as a transcriptional regulator of SNAIL1 expression. HMGA2 also physically interacts with TGF-β/Smad proteins, and this interaction leads to increased Smad binding to the SNAIL1 promoter, cooperatively driving EMT. SNAIL1 knockdown partially reverts HMGA2-induced loss of epithelial differentiation, placing SNAIL1 downstream of HMGA2 in the EMT program. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), promoter-reporter assays, siRNA knockdown with phenotypic readout The Journal of biological chemistry High 18832382
2013 HMGA2 activates expression of the TGF-β type II receptor, thereby enhancing TGF-β signaling and promoting EMT-driven invasion and metastasis. In a mouse allograft model, HMGA2 overexpression converted non-metastatic breast cancer cells to metastatic cells that homed to liver. HMGA2 loss of function in a mouse cancer model reduced tumor multiplicity. Mouse allograft model, gain/loss-of-function in vivo experiments, expression analysis Cancer research Medium 23722545
2013 HMGA2 suppresses TET1 expression; depletion of HMGA2 induces TET1, which then binds and demethylates its own promoter and HOXA gene promoters (including HOXA7 and HOXA9), enhancing their expression and suppressing breast tumor growth and metastasis. ChIP, bisulfite sequencing, xenograft mouse model, shRNA knockdown, genetically engineered mouse model Proceedings of the National Academy of Sciences of the United States of America High 23716660
2013 HMGA2 inhibits expression of miR-200b; miR-200b directly inhibits lysyl oxidase (LOX) expression, leading to decreased invasion. HMGA2 also inhibits syndecan-2 (SDC2) expression; SDC2 depletion induces apoptosis and suppresses breast tumor growth and metastasis. These pathways are downstream of the metastasis suppressor RKIP. Human breast tumor cell lines, MMTV-Wnt mouse model, xenograft assays, gene expression analysis Oncogene Medium 23975428
2006 HMGA2 promotes pituitary adenoma development through acetylation of E2F1 and displacement of HDAC1 from the pRB/E2F1 inhibitory complex, leading to enhanced E2F1 transcriptional activity. Genetic cross of HMGA2 transgenic mice with E2F1 knockout mice confirmed that E2F1 activation is the main mechanism of HMGA2-induced pituitary adenoma. Transgenic and knockout mouse genetics (epistasis), molecular characterization of pRB/E2F1/HDAC1 complex Cell cycle (Georgetown, Tex.) Medium 16969098
2000 HMGIC (HMGA2) plays a role in adipocyte/fat-cell proliferation in vivo: Hmgic-/- mice resist diet-induced obesity and show reduced fat mass in a leptin-deficiency (ob/ob) model in a gene-dose-dependent manner, establishing HMGA2 as required for normal adipogenesis. Knockout and transgenic mouse models, genetic interaction with leptin-deficiency (ob/ob) mutation Nature genetics High 10742101
2016 HMGA2 is required for C/EBPβ-mediated transcriptional activation of PPARγ (Pparγ2) during adipogenesis. HMGA2 co-localizes with C/EBPβ in the nucleus and is required for recruitment of C/EBPβ to the Pparγ2 promoter. HMGA2 and C/EBPβ cooperatively enhance Pparγ2 promoter activity. ChIP, luciferase reporter assay, Co-IP/co-localization, siRNA knockdown and overexpression in 3T3-L1 preadipocytes Biochemical and biophysical research communications High 26966068
2014 HMGA2 functions as a replication fork chaperone in embryonic stem cells (ESCs) and cancer cells, protecting stalled replication forks from endonucleolytic collapse. This function likely involves scaffold formation at branched DNA via multiple DNA-binding AT-hook domains, and HMGA2 works independently of other human factors to prevent DNA strand breaks in two heterologous cell systems. In vitro DNA-binding assays, heterologous cell systems, measurement of DNA strand breaks upon replication stress, functional domain analysis Cell reports High 24508460
2017 HMGA2 binds to supercoiled DNA plectonemes at the lowest concentration (among ds DNA, ss DNA, forked DNA, and supercoiled DNA structures) and transiently stabilizes supercoiled plectonemes against relaxation by type I topoisomerase, suggesting a mechanism by which HMGA2 attenuates fork regression and collapse during replication stress. In vitro DNA-binding assays with four DNA structures, topoisomerase relaxation assays Scientific reports High 28814752
2019 High HMGA2 levels protect cancer cells against DNA breaks triggered by the TOP1 poison irinotecan (likely via DNA supercoil constraining and exclusion of TOP1 from supercoiled DNA), while low-to-moderate HMGA2 levels paradoxically potentiate irinotecan-induced DNA breaks by enhancing drug-target interactions in ternary complexes with supercoiled DNA. Subtelomeric regions are particularly vulnerable to this TOP1 poisoning. Cell-based and in vitro assays, patient-derived xenografts, DNA break quantification, in vitro ternary complex formation assays PloS one Medium 31067275
2018 HMGA2 forms a protein complex with p53 (via its three AT-hook domains, aa 1–83, binding to the tetramerization domain of p53, aa 294–393) and directly binds MDM2 (via MDM2 central acidic and zinc finger domains, aa 111–360). HMGA2 promotes MDM2-mediated ubiquitination and proteasomal degradation of p53, thereby facilitating cell cycle progression and inhibiting apoptosis in colorectal cancer. Co-immunoprecipitation, domain mapping by deletion mutants, ubiquitination assays, Hmga2 knock-in mouse model with chemical carcinogen-induced tumorigenesis The Journal of pathology High 30175854
2017 HMGA2 directly binds to the Twist1 promoter and induces Twist1 expression, leading to upregulation of VE-cadherin and promotion of vasculogenic mimicry in gastric carcinoma. Twist1 knockdown in HMGA2-overexpressing cells reduces VE-cadherin expression. Luciferase reporter assay, Co-IP, ChIP, gain/loss-of-function in vitro and in vivo Scientific reports High 28533522
2017 HMGA2 directly binds the promoter sequence of the Atg10 gene (demonstrated by ChIP), modulating Atg12-Atg5 conjugation and thereby regulating autophagosome formation. HMGA2 knockdown blocks Cr(VI)-induced autophagy, and HMGA2 overexpression induces autophagy markers. ChIP assay, siRNA knockdown, overexpression in HEK293 and HeLa cells, Western blot, in vivo mouse model International journal of cancer Medium 28510366
2015 HMGA2 promotes AML cell proliferation through activation of the PI3K/Akt/mTOR signaling pathway: HMGA2 knockdown in AML cells decreases pAkt and pmTOR protein levels, inhibiting cell proliferation. FISH, qRT-PCR, Western blot, XTT/colony-forming/BrdUrd assays, flow cytometry, xenograft tumor model Journal of cancer research and clinical oncology Medium 26319392
2020 HMGA2 promotes angiogenesis in uterine leiomyoma by upregulating angiogenic factors (VEGFA, EGF, bFGF, TGFα, VEGFR1, VEGFR2) and activating IGF2BP2-mediated pAKT signaling. Silencing IGF2BP2 reduces pAKT levels and decreases endothelial cell (HUVEC) migration. Cell line overexpression, HUVEC migration/tube formation assays, xenograft in vivo, siRNA knockdown, Western blot Fertility and sterility Medium 32868105
2014 HMGA2 is an upstream activator of PLAG1: forced overexpression of HMGA2 in MCF-7 cells induces PLAG1 expression within 24–48 hours, and FGF1-stimulated HMGA2 induction in adipose tissue-derived stem cells leads to simultaneous PLAG1 mRNA increase. All uterine leiomyomas with HMGA2 overexpression also show PLAG1 activation without detectable chromosome 8 abnormalities. Transient transfection/overexpression, qPCR, expression correlation in human tumor samples PloS one Medium 24516594
2016 HMGA2 is required for normal neural crest cell (NCC) specification and development in Xenopus laevis. Hmga2 knockdown disrupts major skeletal derivatives of anterior NCCs and compromises subsequent EMT and migration. Within the NCC genetic network, hmga2 acts downstream of msx1 and is required for msx1, pax3, and snail2 activities. Morpholino knockdown in Xenopus embryos, in situ hybridization, epistasis analysis, breast cancer EMT cell model Developmental biology Medium 26806704
2022 In the Lin28a-Let7 axis in cartilage, Lin28a overexpression upregulates HMGA2 (by inhibiting Let-7 miRNA), and HMGA2 in turn activates SOX9 transcription to promote chondrocyte reprogramming and protect against cartilage breakdown. HMGA2 siRNA knockdown inhibits the cartilage-protective effects of Lin28a overexpression, establishing HMGA2 as an essential mediator in this pathway. Conditional cartilage-specific knockout and overexpression mouse models, RNA-sequencing, siRNA knockdown, OA mouse model Science advances High 36026443
2019 The HMGA2/IMP2 (IGF2BP2) pathway promotes granulosa cell (GC) proliferation in PCOS. HMGA2 and IMP2 are both highly expressed in GCs from PCOS women; HMGA2 regulates IMP2, which in turn regulates Cyclin D2 and SERPINE1 mRNA binding protein 1. Confirmed by luciferase assays and RNA binding protein immunoprecipitation. qRT-PCR in patient GCs, luciferase assays, RNA binding protein immunoprecipitation, overexpression/knockdown proliferation assays The Journal of clinical endocrinology and metabolism Medium 30247605
2020 HMGA2 activates GPX4 expression through transcriptional regulation: HMGA2 binds to the GPX4 gene promoter and promotes cis-element modification by enhancing H3K4 methylation and H3K27 acetylation (enhancer activity). HMGA2 also stimulates GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes, thereby alleviating ferroptotic cell death in pancreatic cancer cells. ChIP (H3K4me and H3K27ac), promoter reporter assays, mTORC1 inhibition, xenograft in vivo, gain/loss-of-function in pancreatic cancer cells Cell death & disease High 38493165
2014 HMGA2 regulates self-renewal of late retinal progenitor cells (RPCs): Hmga2 expression decreases as progenitors exhaust during retinal development, and Hmga2 perturbation (in vitro and in vivo) reveals that Hmga2 functionally mediates cell-extrinsic (endothelial cell) influences on late-RPC self-renewal and multipotentiality. In vitro clonal propagation assays, in vivo retinal analysis, Hmga2 overexpression/knockdown Development (Cambridge, England) Medium 25336737
1996 The HMGIC (HMGA2) gene has a genomic structure of five exons spanning >60 kb, encoding a protein with three AT-hook DNA-binding domains (exons 1–3) and an acidic C-terminal domain (exons 4–5). In lipomas with 12q14-q15 rearrangements, the gene is disrupted specifically in intron 3 (>25 kb), separating the DNA-binding domains from the acidic domain, identifying this intron as the translocation breakpoint hotspot. YAC subcloning, lambda genomic cloning, Southern blotting, Northern blotting Genomics High 8824803
1996 The murine Hmgi-c (HMGA2) protein has three consecutive AT-hook DNA-binding domains and an acidic domain, each encoded by individual exons—an organization conserved from insects to mammals. The gene spans >110 kb with five exons and encodes a 4.1 kb transcript/12 kDa protein. The HMGI-C protein does not function as a typical transcriptional activator but as an architectural factor. Genomic cloning, Northern analysis, protein structural analysis, developmental expression profiling Nucleic acids research High 8918814
1999 HMGIC (HMGA2) promoter activity is regulated by serum/growth factor stimulation. FGF-1 and PDGF-BB are strong inducers of HMGIC expression, acting via both the PI-3 kinase and MAP kinase pathways. In quiescent 3T3-L1 preadipocytes, HMGIC is expressed at low levels but is dramatically upregulated by serum as a delayed-early response gene. Promoter-reporter assays, PI-3 kinase and MAPK pathway inhibitor experiments, Northern blot, growth factor stimulation experiments Oncogene Medium 10490844
2020 HMGA2 is an intrinsically disordered protein (IDP) that can form homodimers in solution. Its AT-hook DNA-binding motifs specifically bind to the minor groove of AT-rich DNA sequences and induce DNA-bending. Biochemical and biophysical studies (IDP characterization, dimerization assays, DNA-binding assays) International journal of molecular sciences Medium 32466162
2020 Suramin inhibits HMGA2-DNA interactions by binding to the AT-hook DNA-binding motifs, preventing HMGA2 from binding to the minor groove of AT-rich DNA sequences. Charge-charge interactions and hydrogen bonding between suramin's sulfonated groups and Arg/Lys residues in the AT-hook motifs are critical for this binding. AlphaScreen ultra-high-throughput screening, biochemical and biophysical binding assays, compound library screening Scientific reports Medium 33139812
2001 In uterine leiomyomas with t(12;14), RAD51L1 is fused to HMGIC (HMGA2), producing chimeric transcripts where exon 7 of RAD51L1 is fused in frame to either exon 2 or exon 3 of HMGIC. The fusion proteins contain RAD51L1 nucleotide binding domains and HMGIC lacking N-terminal AT-hook motifs. RT-PCR of primary tumor samples, sequence analysis of fusion transcripts Genes, chromosomes & cancer Medium 11135437
2015 A 7 bp intronic deletion in HMGA2 affects normal splicing, causing HMGA2 haploinsufficiency associated with Silver-Russell syndrome (SRS) growth phenotype in humans, establishing HMGA2 loss-of-function as causative for SRS-like growth retardation. Sequencing, splicing assay demonstrating aberrant splicing of HMGA2 transcript Journal of human genetics Medium 25809938
2016 HMGA2 sustains glioma-initiating cell (GIC) self-renewal and tumorigenicity by enabling expression of FOXM1 and PLAU. Depletion of HMGA2 in GICs results in compromised self-renewal, tumorigenic capability, and mesenchymal/pericyte differentiation, both in vitro and in vivo. shRNA knockdown in GIC lines, in vitro self-renewal assays, in vivo gliomagenesis model, gene expression analysis Oncotarget Medium 27259253

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Rhizobium lipo-chitooligosaccharide nodulation factors: signaling molecules mediating recognition and morphogenesis. Annual review of biochemistry 500 8811188
2019 Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes. Journal of molecular biology 321 31628942
2008 HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. The Journal of biological chemistry 305 18832382
2013 HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proceedings of the National Academy of Sciences of the United States of America 230 23716660
2013 HMGA2 is a driver of tumor metastasis. Cancer research 224 23722545
2000 In vivo modulation of Hmgic reduces obesity. Nature genetics 173 10742101
1996 LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family. Genomics 170 8812423
2021 HMGA2 as a Critical Regulator in Cancer Development. Genes 162 33668453
2019 Oncological role of HMGA2 (Review). International journal of oncology 139 31432151
2011 Lipo-chitooligosaccharide signaling in endosymbiotic plant-microbe interactions. Molecular plant-microbe interactions : MPMI 134 21469937
2014 MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 131 24390224
2008 HMGA2, microRNAs, and stem cell aging. Cell 127 19070572
1999 HMGIC expression in human adult and fetal tissues and in uterine leiomyomata. Genes, chromosomes & cancer 120 10398424
1997 Expression of reciprocal hybrid transcripts of HMGIC and FHIT in a pleomorphic adenoma of the parotid gland. Cancer research 119 8988031
1998 The expression pattern of the Hmgic gene during development. Genes, chromosomes & cancer 92 9824208
1996 Translocation breakpoints upstream of the HMGIC gene in uterine leiomyomata suggest dysregulation of this gene by a mechanism different from that in lipomas. Genes, chromosomes & cancer 92 8889500
2017 HMGA2 regulates lung cancer proliferation and metastasis. Thoracic cancer 90 28752530
1997 HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas. Oncogene 83 9205100
2013 RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2. Oncogene 81 23975428
2021 m6A modification of circHPS5 and hepatocellular carcinoma progression through HMGA2 expression. Molecular therapy. Nucleic acids 79 34703649
1999 LHFP, a novel translocation partner gene of HMGIC in a lipoma, is a member of a new family of LHFP-like genes. Genomics 79 10329012
2003 Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 73 14614053
2002 Translocation, deletion/amplification, and expression of HMGIC and MDM2 in a carcinoma ex pleomorphic adenoma. The American journal of pathology 70 11839563
2001 Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva. Genes, chromosomes & cancer 64 11550285
2003 HMGA2 expression in uterine leiomyomata and myometrium: quantitative analysis and tissue culture studies. Genes, chromosomes & cancer 63 12874787
2016 Overexpression of HMGA2 promotes tongue cancer metastasis through EMT pathway. Journal of translational medicine 60 26818837
2013 HMGA2 and high-grade serous ovarian carcinoma. Journal of molecular medicine (Berlin, Germany) 58 23686260
1996 Genomic structure and expression of the murine Hmgi-c gene. Nucleic acids research 58 8918814
2020 Overexpression of HMGA2 in breast cancer promotes cell proliferation, migration, invasion and stemness. Expert opinion on therapeutic targets 56 32172636
2010 HMGA2: A pituitary tumour subtype-specific oncogene? Molecular and cellular endocrinology 56 20347930
2019 miR-330 suppresses EMT and induces apoptosis by downregulating HMGA2 in human colorectal cancer. Journal of cellular physiology 55 31241772
2015 Amplified HMGA2 promotes cell growth by regulating Akt pathway in AML. Journal of cancer research and clinical oncology 52 26319392
2016 HMGA2 promotes adipogenesis by activating C/EBPβ-mediated expression of PPARγ. Biochemical and biophysical research communications 51 26966068
2016 The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma. Cancer letters 51 27102002
2019 The HMGA2-IMP2 Pathway Promotes Granulosa Cell Proliferation in Polycystic Ovary Syndrome. The Journal of clinical endocrinology and metabolism 49 30247605
1999 Regulation of HMGIC expression: an architectural transcription factor involved in growth control and development. Oncogene 49 10490844
2010 In vivo modulation of HMGA2 expression. Biochimica et biophysica acta 48 20123068
1998 Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma. Cancer genetics and cytogenetics 47 9772904
2020 High Mobility Group AT-Hook 2 (HMGA2) Oncogenicity in Mesenchymal and Epithelial Neoplasia. International journal of molecular sciences 46 32365712
1997 Molecular characterization of a complex chromosomal rearrangement in a pleomorphic salivary gland adenoma involving the 3'-UTR of HMGIC. Cancer genetics and cytogenetics 46 9169041
2020 HMGA2-mediated tumorigenesis through angiogenesis in leiomyoma. Fertility and sterility 45 32868105
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 HMGA2 promotes breast cancer metastasis by modulating Hippo-YAP signaling pathway. Cancer biology & therapy 43 33307962
2021 Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer's Disease. International journal of molecular sciences 41 34502369
2017 HMGA2 promotes vasculogenic mimicry and tumor aggressiveness by upregulating Twist1 in gastric carcinoma. Scientific reports 41 28533522
2021 MiR-142-3p targets HMGA2 and suppresses breast cancer malignancy. Life sciences 40 33785332
1998 The high mobility group protein, HMGI-C. The international journal of biochemistry & cell biology 40 9722980
1996 Genomic characterization of human HMGIC, a member of the accessory transcription factor family found at translocation breakpoints in lipomas. Genomics 40 8824803
2006 Critical role of the HMGA2 gene in pituitary adenomas. Cell cycle (Georgetown, Tex.) 39 16969098
2019 HMGA2 and Bach-1 cooperate to promote breast cancer cell malignancy. Journal of cellular physiology 38 30825204
2014 Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells. Cell reports 38 24508460
2020 Emerging roles for HMGA2 in colorectal cancer. Translational oncology 37 33069103
1998 Cloning and molecular characterization of part of a new gene fused to HMGIC in mesenchymal tumors. The American journal of pathology 37 9466569
2017 Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer. Theranostics 36 29109785
2015 MiR-204 regulates HMGA2 expression and inhibits cell proliferation in human thyroid cancer. Cancer biomarkers : section A of Disease markers 36 26406941
2014 Hmga2 regulates self-renewal of retinal progenitors. Development (Cambridge, England) 36 25336737
2005 Fusion of the HMGA2 and NFIB genes in lipoma. Virchows Archiv : an international journal of pathology 36 16133369
2018 HMGA2 and MED12 alterations frequently co-occur in uterine leiomyomas. Gynecologic oncology 35 30017537
2015 A splicing mutation of the HMGA2 gene is associated with Silver-Russell syndrome phenotype. Journal of human genetics 35 25809938
2001 Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma. Genes, chromosomes & cancer 35 11135437
2024 HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells. Cell death & disease 34 38493165
2001 Ectopic sequences from truncated HMGIC in liposarcomas are derived from various amplified chromosomal regions. Genes, chromosomes & cancer 34 11391797
2006 Truncation and fusion of HMGA2 in lipomas with rearrangements of 5q32-->q33 and 12q14-->q15. Cytogenetic and genome research 33 16276091
2024 HMGA2 promotes cancer metastasis by regulating epithelial-mesenchymal transition. Frontiers in oncology 32 38361784
2022 Lin28a induces SOX9 and chondrocyte reprogramming via HMGA2 and blunts cartilage loss in mice. Science advances 32 36026443
2018 Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance. Scientific reports 32 30228296
2001 Gene fusion involving HMGIC is a frequent aberration in uterine leiomyomas. Journal of human genetics 32 11450849
2000 Novel gene fusion of COX6C at 8q22-23 to HMGIC at 12q15 in a uterine leiomyoma. Genes, chromosomes & cancer 32 10679920
2023 HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response. Pharmacological research 31 36931542
2021 HMGA2 Supports Cancer Hallmarks in Triple-Negative Breast Cancer. Cancers 31 34680349
2021 Circular RNA 100146 Promotes Colorectal Cancer Progression by the MicroRNA 149/HMGA2 Axis. Molecular and cellular biology 30 33257506
2015 The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell tumorigenicity. Journal of neuropathology and experimental neurology 30 25575139
2020 The Mammalian High Mobility Group Protein AT-Hook 2 (HMGA2): Biochemical and Biophysical Properties, and Its Association with Adipogenesis. International journal of molecular sciences 29 32466162
2014 Correlated expression of HMGA2 and PLAG1 in thyroid tumors, uterine leiomyomas and experimental models. PloS one 29 24516594
1998 HMGIC expression patterns in non-small lung cancer and surrounding tissue. Anticancer research 29 9858904
2017 HMGA2 plays an important role in Cr (VI)-induced autophagy. International journal of cancer 28 28510366
2021 Optimizing pDNA Lipo-polyplexes: A Balancing Act between Stability and Cargo Release. Biomacromolecules 27 33616407
2022 Development of Lipo-γ-AA Peptides as Potent Antifungal Agents. Journal of medicinal chemistry 26 35637173
2020 HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma. Cell death & disease 26 32719345
2016 HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells. Oncotarget 26 27259253
2020 Identification of HMGA2 inhibitors by AlphaScreen-based ultra-high-throughput screening assays. Scientific reports 25 33139812
2018 HMGA2 promotes intestinal tumorigenesis by facilitating MDM2-mediated ubiquitination and degradation of p53. The Journal of pathology 25 30175854
2020 Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression. Cancers 24 33374674
2019 Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas. NPJ breast cancer 24 30675516
2017 Oncofetal HMGA2 effectively curbs unconstrained (+) and (-) DNA supercoiling. Scientific reports 24 28814752
2020 MEG3/MIR-376B-3P/HMGA2 axis is involved in pituitary tumor invasiveness. Journal of neurosurgery 23 31899875
2017 Lipo-Oligomer Nanoformulations for Targeted Intracellular Protein Delivery. Biomacromolecules 23 28649842
2016 Hmga2 is required for neural crest cell specification in Xenopus laevis. Developmental biology 23 26806704
2023 Unraveling the Roles of miR-204-5p and HMGA2 in Papillary Thyroid Cancer Tumorigenesis. International journal of molecular sciences 21 37445942
2015 Lipo-chitooligosaccharidic nodulation factors and their perception by plant receptors. Glycoconjugate journal 21 26233756
2023 Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis. Frontiers in pharmacology 20 36937888
2020 Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB. Genes, chromosomes & cancer 20 32654217
2018 MiR‑495 suppresses cell proliferation by directly targeting HMGA2 in lung cancer. Molecular medicine reports 20 30569167
2018 HMGA2, but not HMGA1, is overexpressed in human larynx carcinomas. Histopathology 19 29266325
2016 HMGA2 is associated with the aggressiveness of tongue squamous cell carcinoma. Oral diseases 19 27809392
2020 HMGA2 Variants in Silver-Russell Syndrome: Homozygous and Heterozygous Occurrence. The Journal of clinical endocrinology and metabolism 18 32421827
2020 MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway. Journal of orthopaedic surgery and research 18 33168056
2015 HMGA2 expression pattern and TERT mutations in tumors of the vulva. Oncology reports 18 25823555
2019 The chromatin structuring protein HMGA2 influences human subtelomere stability and cancer chemosensitivity. PloS one 17 31067275
2002 HMGIC alterations in smooth muscle tumors of soft tissues and other sites. Cancer genetics and cytogenetics 17 12419585

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