Affinage

INHBA

Inhibin beta A chain · UniProt P08476

Length
426 aa
Mass
47.4 kDa
Annotated
2026-04-28
73 papers in source corpus 30 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INHBA encodes the inhibin βA subunit, which homodimerizes to form activin A, a secreted TGF-β superfamily ligand that signals through SMAD2/3 to regulate cell proliferation, epithelial-mesenchymal transition, fibroblast activation, macrophage polarization, and immune evasion across diverse tissue contexts (PMID:10932194, PMID:30963572, PMID:31827640, PMID:38360876). Activin A drives cancer-associated fibroblast activation via paracrine SMAD2 signaling, induces PD-L1 expression on fibroblasts, promotes Treg differentiation, and suppresses IFN-γ-dependent CD8+ T cell recruitment through downregulation of CXCL9/CXCL10, thereby shaping an immunosuppressive tumor microenvironment (PMID:28814667, PMID:38360876, PMID:39223366). In neurons, nuclear calcium signaling downstream of synaptic NMDA receptors transcriptionally induces INHBA, and the resulting activin A reduces extrasynaptic NMDA receptor-mediated calcium influx to confer neuroprotection against excitotoxicity and ischemic injury (PMID:26279570, PMID:41339520). INHBA mRNA stability is post-transcriptionally regulated by IGF2BP1 in an m6A-dependent manner and by HuR, while its transcription is controlled by SPI1, C/EBPβ, GLI1, and KAT8, and it is repressed by multiple miRNAs including miR-146a, miR-211, miR-130b-3p, and miR-342-3p (PMID:37644505, PMID:35338119, PMID:27541693, PMID:40132395, PMID:41540191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Knock-in of Inhbb into the Inhba locus demonstrated that most Inhba-null phenotypes (craniofacial defects) arise from spatial/temporal expression differences rather than ligand-receptor specificity, while also revealing activin A-specific roles in somatic and gonadal tissues that Inhbb cannot substitute.

    Evidence Gene knock-in rescue in mice with dosage analysis

    PMID:10932194

    Open questions at the time
    • Molecular basis of activin A-specific (non-rescuable) functions undefined
    • Receptor-level selectivity versus co-receptor usage not resolved
  2. 2009 Medium

    Activin A was established as a proliferative signal in epithelial cancer cells, with INHBA expression shown to be epigenetically regulated through promoter methylation and histone acetylation, providing the first mechanistic link between epigenetic derepression and activin-driven tumor growth.

    Evidence Exogenous activin A, follistatin inhibition, INHBA siRNA, and 5-AZA/TSA treatment in esophageal adenocarcinoma cells

    PMID:19240652

    Open questions at the time
    • Specific histone marks and demethylases at INHBA promoter not identified
    • In vivo validation of epigenetic regulation lacking
  3. 2015 High

    A neuroprotective circuit was delineated in which BDNF-activated synaptic NMDA receptors trigger nuclear calcium signaling to induce INHBA transcription, and the resulting activin A attenuates extrasynaptic NMDA receptor calcium influx, protecting neurons from excitotoxicity and ischemic injury.

    Evidence Nuclear calcium blockade, Inhba siRNA, recombinant activin A rescue, calcium imaging, mouse stroke model

    PMID:26279570

    Open questions at the time
    • Mechanism by which activin A reduces extrasynaptic NMDA receptor activity not defined at the molecular level
    • Downstream transcriptional targets in neurons not identified
  4. 2016 Medium

    INHBA was placed as a downstream effector of miR-146a in macrophage polarization, showing that activin A promotes M1 and suppresses M2 macrophage markers — the first direct evidence for INHBA controlling innate immune cell phenotype via a specific miRNA regulatory input.

    Evidence 3′-UTR luciferase reporter, miR-146a overexpression/knockdown, INHBA rescue in macrophages

    PMID:27541693

    Open questions at the time
    • Signaling pathway downstream of INHBA in macrophage polarization not specified
    • In vivo relevance not tested
  5. 2017 Medium

    INHBA was identified as a key paracrine mediator linking adrenergic stress to cancer-associated fibroblast activation, establishing the concept that tumor cell-derived activin A remodels the stroma.

    Evidence Restraint-stress model, β-blocker treatment, INHBA ablation in ovarian cancer in vitro and in vivo

    PMID:28814667

    Open questions at the time
    • Adrenergic receptor subtype and transcriptional pathway leading to INHBA induction not defined
    • Whether fibroblast activation is SMAD-dependent not tested in this study
  6. 2019 Medium

    SMAD2 was identified as the required downstream effector of INHBA-mediated fibroblast activation in ovarian cancer, and INHBA knockdown in gastric cancer confirmed TGF-β pathway dependence for proliferation, migration, and invasion, solidifying SMAD2/3 as the canonical intracellular pathway for activin A's pro-tumorigenic effects.

    Evidence INHBA knockdown, Smad2 pathway inhibition, tumor xenografts in gastric and ovarian cancer

    PMID:30963572 PMID:31827640

    Open questions at the time
    • Non-SMAD signaling contributions (e.g., MAPK, PI3K) not excluded
    • Identity of activin receptor complexes on fibroblasts not characterized
  7. 2020 Medium

    miR-211 was shown to directly repress INHBA, and its loss led to enhanced TGF-β/Smad2/3 activation and cancer stemness in prostate cancer, adding a second miRNA regulatory axis and linking INHBA to stem cell properties.

    Evidence miR-211 overexpression/knockdown, INHBA siRNA, sphere-forming assay, in vivo tumor model

    PMID:33223523

    Open questions at the time
    • Mechanism by which INHBA/activin A promotes stemness transcription factors unknown
    • Interaction with androgen receptor signaling not tested
  8. 2021 Medium

    INHBA was demonstrated to induce EMT in breast cancer and to be a necessary factor in PEAK1+ mesenchymal stromal cell conditioned medium conferring lapatinib resistance, establishing activin A as a mediator of both intrinsic motility programs and therapy resistance through stromal interactions.

    Evidence INHBA overexpression/silencing for EMT markers; conditioned medium depletion identifying INHBA as required for PEAK1-mediated lapatinib resistance; metabolic profiling showing glycolysis dependence

    PMID:34239043 PMID:34346300 PMID:35248133

    Open questions at the time
    • Direct receptor engagement on cancer cells not shown
    • Whether EMT and drug resistance share the same SMAD pathway branch unclear
  9. 2022 Medium

    Post-transcriptional regulation of INHBA mRNA was mechanistically defined: circTHBS1 sponges miR-204-5p to de-repress INHBA, and additionally recruits HuR to stabilize INHBA mRNA, connecting non-coding RNA networks to INHBA-driven TGF-β activation in gastric cancer. Separately, metformin was shown to suppress INHBA to block PI3K/Akt/cyclin D1 and induce G1/S arrest in colorectal cancer.

    Evidence RNA pull-down, RIP, luciferase reporter for circTHBS1/miR-204-5p/HuR axis; INHBA knockdown/overexpression with metformin and cell cycle analysis

    PMID:35236827 PMID:35338119

    Open questions at the time
    • Whether HuR binding is m6A-dependent or independent not resolved
    • Metformin's direct target leading to INHBA suppression not identified
  10. 2023 High

    IGF2BP1 was identified as an m6A-dependent stabilizer of INHBA mRNA that cooperates with G3BP1, directly linking epitranscriptomic regulation to INHBA protein output and Smad2/3-driven invasion in esophageal squamous cell carcinoma. Separately, a miR-130b-3p/INHBA/IL-8 axis was shown to control angiogenesis in diabetic ischemia.

    Evidence RIP-seq, RNA pulldown, m6A-specific PCR, BTYNB inhibitor for IGF2BP1; miR-130b mimic in vivo in ischemic limb model

    PMID:37097749 PMID:37644505

    Open questions at the time
    • Specific m6A writer depositing marks on INHBA mRNA not identified
    • Whether IGF2BP1 and HuR compete or cooperate on INHBA mRNA unclear
  11. 2024 High

    INHBA's immunoregulatory functions were resolved at two levels: in cancer-associated fibroblasts, activin A induces autocrine PD-L1 via SMAD2 and promotes Treg differentiation through cell contact; in tumor cells, INHBA suppresses IFN-γ signaling to reduce CXCL9/CXCL10 and impair CD8+ T cell infiltration, explaining resistance to anti-PD-L1 therapy that is reversible by activin A neutralization.

    Evidence INHBA knockdown in CAFs, T cell co-culture, anti-activin A antibody in vivo, spatial transcriptomics; Inhba gain/loss-of-function across four syngeneic tumor models with IFN-γ pathway analysis

    PMID:38360876 PMID:39223366

    Open questions at the time
    • Whether SMAD2-dependent PD-L1 induction and IFN-γ suppression are the same or distinct mechanisms is unresolved
    • Activin receptor expression pattern across immune cell subsets not characterized
  12. 2024 Medium

    Transcriptional regulation of INHBA was mapped: GLI1 directly activates INHBA transcription, and Smad-mediated feedback transcriptionally reactivates GLI1, creating a positive feedback loop in gastric cancer; FAP+ mesenchymal stromal cells secrete INHBA to activate SMAD2/3 in neighboring cancer cells.

    Evidence ChIP and reporter assays for GLI1; ELISA and conditioned medium with FAP+ sorted stromal cells; in vivo gastric cancer models

    PMID:38676428 PMID:39615112

    Open questions at the time
    • How the GLI1/INHBA feedback loop is initiated and terminated not defined
    • Relative contribution of stromal vs. tumor-intrinsic INHBA unclear
  13. 2025 Medium

    Multiple transcriptional inputs to INHBA were confirmed: SPI1 binds the INHBA promoter to drive CCL2-mediated macrophage recruitment, and C/EBPβ activates INHBA to establish a PI3K/AKT/TGF-β positive feedback loop, while KAT8 deficiency de-represses INHBA contributing to vascular senescence through TGF-β/P15 signaling.

    Evidence ChIP and dual-luciferase reporters for SPI1 and C/EBPβ; CRISPR KAT8 KO with multi-omics in endothelial cells and mice

    PMID:40132395 PMID:41445196 PMID:41540191

    Open questions at the time
    • How multiple transcription factors (SPI1, C/EBPβ, GLI1, KAT8) are hierarchically organized at the INHBA promoter is unknown
    • Chromatin state and enhancer architecture at the INHBA locus not mapped
  14. 2025 Medium

    A non-canonical intracellular function for INHBA protein was uncovered: INHBA binds CTPS1 and competitively inhibits SMURF1-mediated ubiquitination of CTPS1, stabilizing it to enhance pyrimidine metabolism and gemcitabine resistance in pancreatic cancer. Additionally, INHBA binds ITGA6 to activate MAPK signaling in gastric cancer, and interacts with COL10A1 to activate PI3K/AKT in prostate cancer.

    Evidence IP-mass spectrometry, co-IP, ubiquitination assay, BTYNB for CTPS1 axis; co-IP and rescue for ITGA6/MAPK and COL10A1/PI3K/AKT

    PMID:39656597 PMID:41239468 PMID:41799510

    Open questions at the time
    • Whether INHBA–CTPS1 interaction occurs intracellularly or extracellularly is unclear
    • INHBA interaction with ITGA6 and COL10A1 each shown by single-lab co-IP without reciprocal or structural validation
    • Relationship between these non-canonical interactions and classical activin receptor signaling not clarified
  15. 2025 Medium

    Extrasynaptic NMDA receptor activation suppresses Inhba transcription in hippocampal neurons, and pharmacological restoration (memantine, FP802) of Inhba expression attenuated neurodegeneration in a Huntington's disease mouse model, extending the neuroprotective role of INHBA beyond ischemia to chronic neurodegeneration.

    Evidence Pharmacological esNMDAR activation, memantine and FP802 treatment, HD mouse model, transcriptomic profiling

    PMID:41339520

    Open questions at the time
    • Whether activin A protein levels and secretion are restored in vivo not measured
    • Downstream neuroprotective effectors of activin A in HD context not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of activin A interactions with non-canonical partners (CTPS1, ITGA6, COL10A1); how multiple transcription factors and post-transcriptional regulators are integrated at the INHBA locus in different cell types; the relative contributions of autocrine versus paracrine activin A signaling in the tumor microenvironment; and whether the intracellular/non-canonical functions of INHBA protein are independent of its secreted ligand role.
  • No structural data for INHBA interactions with CTPS1, ITGA6, or COL10A1
  • Relative autocrine vs. paracrine contribution of INHBA in tumors not quantified
  • Whether intracellular INHBA functions require dimerization is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 8 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1643685 Disease 6 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 2
Partners
COL10A1CTPS1ELAVL1G3BP1IGF2BP1ITGA6SMAD2SMAD3
Complex memberships
Activin A (βA homodimer)Activin AB (βA/βB heterodimer)Inhibin A (α/βA heterodimer)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Inhba encodes the βA subunit of activin A (homodimer) and activin AB (heterodimer with βB). Knock-in of Inhbb into the Inhba locus rescued craniofacial (whisker, palate, tooth) phenotypes of Inhba-null mice, demonstrating that spatial/temporal expression differences—not receptor specificity—underlie most Inhba-null phenotypes; novel somatic and gonadal phenotypes revealed additional activin A-specific functions. Gene knock-in (Inhbb coding region inserted into Inhba locus), genetic rescue experiment in mice, loss-of-function and dosage analysis Nature genetics High 10932194
2015 BDNF activates synaptic NMDA receptors, triggering nuclear-calcium signaling that transcriptionally upregulates Inhba (inhibin β-A). The resulting activin A reduces extrasynaptic NMDA-receptor-mediated calcium influx, protecting neurons from mitochondrial dysfunction and excitotoxicity. This nuclear-calcium–Inhba pathway confers neuroprotection against ischemic damage in a mouse stroke model. Nuclear calcium signaling blockade, siRNA knockdown of Inhba, recombinant activin A rescue, mouse stroke model (in vivo), calcium imaging Cell reports High 26279570
2019 INHBA silencing in gastric cancer cells inactivates the TGF-β signaling pathway, inhibiting cell migration, invasion, and proliferation, and reduces tumor xenograft growth in nude mice, placing INHBA upstream of TGF-β signaling in gastric cancer progression. shRNA-mediated INHBA knockdown, migration/invasion assays, tumor xenograft model in nude mice, pathway gene expression analysis Journal of cellular physiology Medium 30963572
2009 Exogenous activin A (INHBA homodimer) promotes proliferation of esophageal adenocarcinoma cell lines, while follistatin (activin inhibitor) or INHBA-targeting siRNA reduces proliferation. INHBA expression in EAC cell lines is epigenetically regulated via promoter demethylation and histone acetylation (treatment with 5-AZA and trichostatin A upregulates INHBA mRNA and protein). Exogenous activin A treatment, follistatin inhibition, siRNA knockdown, 5-AZA/trichostatin A epigenetic treatment, RT-PCR, IHC Journal of thoracic oncology Medium 19240652
2017 Adrenergic signaling induces cancer cell production of INHBA (inhibin βA/activin A), which drives cancer-associated fibroblast (CAF) activation; ablating INHBA decreased the CAF phenotype both in vitro and in vivo in ovarian cancer models. This establishes INHBA as a mediator linking adrenergic stress signals to stromal remodeling. In vivo restraint-stress model, β-blocker pharmacological blockade, INHBA ablation (siRNA/shRNA), CAF activation assays in vitro and in vivo JCI insight Medium 28814667
2016 miR-146a directly targets the 3′-UTR of INHBA to suppress its expression. INHBA overexpression rescued the miR-146a–induced reduction of M1 macrophage markers (IL-6, IL-12, TNF-α) and reversed the miR-146a–induced increase of M2 markers (Arg1, CCL17, CCL22), placing INHBA downstream of miR-146a as a regulator of macrophage polarization. 3′-UTR luciferase reporter assay, miR-146a overexpression/knockdown, INHBA overexpression rescue experiments, macrophage polarization assays Molecular immunology Medium 27541693
2019 INHBA knockdown in ovarian cancer cells impairs cancer xenograft growth by reducing stromal fibroblast activation in vivo. Mechanistically, Smad2 signaling is required for INHBA-induced fibroblast activation, and inhibiting this pathway reverses fibroblast activation. INHBA knockdown in cancer cells, xenograft model, fibroblast co-culture, Smad2 pathway inhibition Disease markers Medium 31827640
2022 CircTHBS1 acts as a competing endogenous RNA (ceRNA) by sponging miR-204-5p, thereby de-repressing INHBA expression. Additionally, circTHBS1 enhances HuR-binding to INHBA mRNA, increasing its stability. Elevated INHBA subsequently activates the TGF-β pathway to promote gastric cancer malignancy. RNA pull-down, luciferase reporter assay, RNA immunoprecipitation (RIP), gain/loss-of-function assays, in vitro and in vivo Cell death & disease Medium 35338119
2022 Metformin specifically suppresses INHBA expression in colorectal cancer cells, blocking activation of TGF-β signaling, which downregulates PI3K/Akt activity and cyclin D1 levels, causing G1/S cell cycle arrest. INHBA knockdown phenocopies metformin's anti-proliferative effect; INHBA overexpression rescues proliferation. INHBA knockdown and overexpression in CRC cells, metformin treatment, cell cycle analysis, PI3K/Akt pathway readouts, Western blot Cell death & disease Medium 35236827
2023 IGF2BP1 binds and stabilizes INHBA mRNA (m6A-dependent), increasing INHBA protein levels and activating Smad2/3 signaling to promote ESCC cell invasion and migration. G3BP1 interacts with IGF2BP1 to co-regulate this pathway. The small-molecule inhibitor BTYNB disrupts IGF2BP1–INHBA interaction and attenuates malignant phenotypes. RIP-seq, RNA pulldown, mass spectrometry, gene-specific m6A PCR, RNA stability assay, siRNA knockdown, immunofluorescence, in vivo metastasis assay Experimental hematology & oncology High 37644505
2024 INHBA/activin A in CAFs induces autocrine PD-L1 expression through SMAD2-dependent signaling. INHBA+ CAFs promote Treg differentiation through direct cell-to-cell contact. In ovarian cancer mouse models, neutralizing activin A antibody attenuated tumor progression and reduced pro-tumorigenic myofibroblast and macrophage infiltration. INHBA knockdown in human ovarian CAFs, T cell/CAF co-culture, activin A neutralizing antibody in vivo, SMAD2 signaling analysis, spatial transcriptomics of patient tumors NPJ precision oncology High 38360876
2024 Tumor-intrinsic INHBA/activin A suppresses the IFN-γ signaling pathway in the tumor microenvironment, leading to reduced IFN-γ-induced PD-L1 expression and decreased CXCL9/CXCL10 chemokine secretion, thereby impairing CD8+ T cell infiltration. INHBA overexpression abolishes anti-PD-L1 efficacy; INHBA deficiency enhances it. Garetosmab (activin A-specific antibody) combined with anti-PD-L1 shows superior anti-tumor effect. Gain/loss-of-function of Inhba in CT26, MC38, B16, 4T1 tumor models; IFN-γ signaling pathway analysis; anti-PD-L1 combination treatment in vivo; TIMER2.0 immune infiltration analysis Acta pharmacologica Sinica Medium 39223366
2020 miR-211 directly targets INHBA (negatively regulating it), and overexpression of miR-211 or knockdown of INHBA reduces TGF-β pathway activation (TGF-β1, TGF-β2, Smad2, Smad3, phospho-Smad2/3) and decreases proliferation, invasion, colony-forming ability, sphere-forming, and stemness of prostate cancer stem cells in vitro and tumor growth in vivo. miR-211 overexpression/knockdown, INHBA siRNA knockdown, in vitro functional assays (proliferation, invasion, colony/sphere forming), in vivo tumor model Cancer gene therapy Medium 33223523
2023 miR-130b-3p directly targets and represses INHBA. miR-130b overexpression or siRNA-mediated knockdown of INHBA induces IL-8 expression (a potent angiogenic chemokine) and promotes revascularization in diabetic ischemic limb models in vivo, establishing a miR-130b/INHBA/IL-8 axis controlling angiogenesis. RNA-Seq, miRNA target prediction algorithms, siRNA knockdown of Inhba, miR-130b mimic delivery in vivo (db/db ischemic mice after FAL), angiogenesis assays, limb necrosis scoring JCI insight Medium 37097749
2021 INHBA induces EMT and accelerates breast cancer cell motility and invasion by activating TGF-β-regulated target genes. INHBA overexpression increases EMT marker expression (e.g., vimentin) and promotes migration; INHBA silencing reverses these effects. INHBA overexpression and siRNA silencing, wound-healing assay, transwell migration assay, EMT marker gene quantification (RT-qPCR, Western blot) Bioengineered Medium 34346300
2021 INHBA knockdown in HER2+ basal breast cancer cells slows growth, increases lapatinib sensitivity, and shifts metabolism from glycolysis to oxidative phosphorylation, reducing tumor invasiveness. INHBA had no effect in luminal HER2+ cells, indicating subtype-specific function. siRNA knockdown screen, 2D and 3D cell culture, metabolic profiling, lapatinib sensitivity assay Breast cancer research Medium 35248133
2021 INHBA in cancer cells interacts with PEAK1-expressing mesenchymal stem cells/CAFs: INHBA/activin A is a necessary secreted factor in PEAK1+ MSC conditioned medium that promotes lapatinib resistance in HER2+ breast cancer, establishing a SNAI2–PEAK1–INHBA stromal axis. Conditioned medium experiments, PEAK1 knockdown, INHBA depletion, single-cell CycIF imaging, bioinformatic secretome analysis Oncogene Medium 34239043
2024 GLI1 transcriptionally upregulates INHBA, and elevated INHBA activates Smad signaling which in turn transcriptionally activates GLI1, forming a positive GLI1/INHBA feedback loop driving gastric cancer progression. Disrupting this interaction inhibits GC tumorigenesis in vivo. Transcriptional reporter assays, gain/loss-of-function, in vivo tumor model, Smad pathway analysis, H. pylori/FTO/YTHDF2/GLI1 m6A pathway analysis Cancer science Medium 38676428
2024 FAP+ gastric cancer mesenchymal stromal cells secrete INHBA by paracrine signaling, activating SMAD2/3 pathway in gastric cancer cells to increase their proliferation and migration. Additionally, FAP+ GCMSCs induce collagen deposition in ECM, which activates Integrin β1 (ITGB1)→FAK→YAP signaling to promote invasion and stemness. ELISA, Western blot, conditioned medium experiments, flow cytometry-sorted FAP+ GCMSCs, transcriptomic sequencing, IHC, Masson staining International immunopharmacology Medium 39615112
2022 miR-342-3p carried by BMSC-derived extracellular vesicles is transferred into breast cancer cells, downregulating INHBA expression. Reduced INHBA then represses IL13Rα2 expression. This INHBA/IL13Rα2 axis mediates BMSC-EV-induced suppression of breast cancer cell proliferation and metastasis in vitro and in vivo. Co-culture of EVs with MCF-7 cells, luciferase reporter assay, RNA pull-down, RIP assay, nude mouse tumorigenicity assay Translational oncology Medium 35093789
2024 COL10A1 directly interacts with INHBA (by co-immunoprecipitation) in prostate cancer cells and facilitates PI3K and AKT phosphorylation. INHBA knockdown reverses the oncogenic effects (proliferation, migration, invasion) of COL10A1 overexpression, indicating INHBA is functionally downstream of COL10A1 in this signaling axis. Immunoprecipitation, Western blot for PI3K/AKT phosphorylation, CCK-8, colony formation, Transwell, flow cytometry, rescue experiment in cells and mouse models Journal of cellular and molecular medicine Medium 39656597
2025 INHBA promotes gemcitabine resistance in pancreatic cancer by binding CTPS1 (cytidine triphosphate synthase 1) and competitively inhibiting SMURF1 (SMAD-specific E3 ubiquitin ligase)-mediated ubiquitination of CTPS1, thereby enhancing CTPS1 stability and promoting pyrimidine metabolism. Immunoprecipitation mass spectrometry, co-IP, ubiquitination assay, drug sensitivity analysis, colony formation, EdU, flow cytometry, xenograft model Cancer cell international Medium 41239468
2025 KAT8 suppresses vascular senescence by regulating the INHBA/TGF-β/P15 signaling axis. KAT8 deficiency upregulates INHBA and exacerbates aging phenotypes; KAT8 overexpression attenuates vascular senescence. Multi-omics (miRNA-seq, ATAC-seq, RNA-seq) shows hsa-miR-339-3p drives age-related KAT8 downregulation. CRISPR-Cas9 loss/gain-of-function in endothelial cells and mice (C57BL/6J, ApoE-/-), multi-omics (miRNA-seq, ATAC-seq, RNA-seq), vascular senescence phenotyping Molecular therapy Medium 41445196
2025 INHBA confers 5-FU chemoresistance in colon cancer cells by facilitating cellular senescence through negative regulation (inactivation) of the Hippo signaling pathway. INHBA downregulation enhances 5-FU sensitivity, reduces senescent cell proportion and IL-6/IL-8 levels; the Hippo inhibitor verteporfin recapitulates INHBA's effects. INHBA knockdown, verteporfin (Hippo inhibitor) treatment, senescence assays (SA-β-gal), cell cycle analysis, xenograft model The international journal of biochemistry & cell biology Medium 38588888
2025 SPI1 transcription factor binds the INHBA promoter and transcriptionally activates INHBA expression in gastric cancer cells. INHBA then activates TGF-β signaling to upregulate CCL2, promoting macrophage recruitment and M2 polarization, which in turn facilitates GC cell proliferation, migration, and invasion. ChIP assay, dual-luciferase reporter, siRNA knockdown of INHBA and SPI1, ELISA for CCL2, macrophage polarization assays, in vivo xenograft Pathology, research and practice Medium 40132395
2025 C/EBPβ transcription factor upregulates INHBA expression in gastric cancer. INHBA promotes M2 macrophage polarization and activates the PI3K/AKT pathway, forming a PI3K/AKT/TGF-β positive feedback loop driving tumor progression and metastasis. ChIP, dual-luciferase reporter, CIBERSORT for immune infiltration, INHBA knockdown/overexpression, in vivo mouse model British journal of cancer Medium 41540191
2025 Extrasynaptic NMDA receptor (esNMDAR) activation extensively suppresses synaptic activity-regulated transcription including Inhba and Bdnf in hippocampal neurons. In a Huntington's disease mouse model, memantine or FP802 (targeting the NMDAR/TRPM4 complex) restored Inhba and Bdnf expression and attenuated the HD disease marker DARPP-32 loss, placing Inhba as a key neuroprotective gene regulated by the esNMDAR/CREB pathway. Primary hippocampal neuron cultures, pharmacological esNMDAR activation, memantine treatment, FP802 targeting NMDAR/TRPM4, HD mouse model, transcriptomic profiling Communications biology Medium 41339520
2025 INHBA promotes gastric cancer progression by targeting ITGA6 (Integrin α6) to activate the MAPK signaling pathway. INHBA and ITGA6 physical interaction was confirmed by Co-IP, and rescue experiments demonstrated that INHBA's pro-tumorigenic effects are mediated through ITGA6/MAPK. RNA-seq, Co-IP, co-immunofluorescence, Western blot, rescue assays, in vivo tumor model, RT-qPCR and IHC in clinical specimens Oncology research Medium 41799510
2022 Dysregulation of Inhba (elevated basal expression) and Npas4 (superinduction after learning) in DBA/2J mice is associated with altered excitation-inhibition balance in CA1 pyramidal neurons (fewer inhibitory, more excitatory miniature postsynaptic currents), linking Inhba expression levels to synaptic function and cognitive deficits. In vivo spatial object recognition task, IEG expression analysis, whole-cell patch-clamp electrophysiology, primary neuronal cultures Learning & memory Low 35042829
2025 In a PCOS mouse model, Inhba is co-expressed with Smad2 and E2f4 in Lrp2-high thecal cells. siRNA-mediated knockdown of Inhba suppresses thecal cell proliferation in vitro (greatest effect among Inhba, Smad2, E2f4 knockdowns), indicating Inhba acts through Smad2 to drive E2f4-dependent cell cycle entry in thecal hyperplasia. Spatial transcriptomics, siRNA knockdown, EdU incorporation, flow cytometry (cell cycle), DHEA-induced PCOS mouse model Frontiers in cell and developmental biology Medium 40831751
2025 Mesenchyme-specific deletion of Gata2 reduces Inhba expression in the epididymal mesenchyme, leading to decreased epithelial proliferation and defective epididymal coiling. Dihydrotestosterone supplementation does not rescue the coiling defect, establishing that mesenchymal Gata2 promotes epididymal development through Inhba induction independently of androgen signaling. Conditional Gata2 knockout (mesenchyme-specific), DHT supplementation rescue experiment, epididymal morphometry, Inhba expression analysis bioRxiv (preprint)preprint Medium
2025 In cochlear progenitor cells, TRIM71 represses Inhba and Tgfbr2 expression. Loss of TRIM71 leads to premature Inhba-mediated TGF-β signaling activation, causing early hair cell differentiation. InhbaTgfbr1 double-knockout mice indicate Inhba maintains hair cell progenitors in a proliferative, undifferentiated state by restricting TGF-β-type signaling. Conditional Trim71 KO in mice, Inhba/Tgfbr1 double-KO, transcriptomic profiling of cochlear progenitor cells, hair cell phenotyping, hearing tests bioRxiv (preprint)preprint Medium
2025 Integrin α2 (Itgα2) links collagen I engagement to INHBA expression induction in basal-like cancer cells, activating TGF-β signaling which upregulates vimentin while preserving epithelial junction gene expression (partial EMT). Itgα2 also promotes ECM degradation through a TGF-β-independent mechanism, identifying an Itgα2→INHBA→TGFβ axis as a regulator of leader cell function in collective invasion. Collagen I-responsive cell subset identification, Itgα2 manipulation, INHBA expression measurement, TGFβ pathway inhibition, vimentin/junction gene expression analysis bioRxiv (preprint)preprint Low

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Nature genetics 162 10932194
2010 Multi-cancer computational analysis reveals invasion-associated variant of desmoplastic reaction involving INHBA, THBS2 and COL11A1. BMC medical genomics 129 21047417
2013 Significance of INHBA expression in human colorectal cancer. Oncology reports 76 24085226
2019 INHBA gene silencing inhibits gastric cancer cell migration and invasion by impeding activation of the TGF-β signaling pathway. Journal of cellular physiology 75 30963572
2015 BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A. Cell reports 75 26279570
2017 The combination of circulating long noncoding RNAs AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1 fragments in plasma serve as diagnostic markers for gastric cancer. Oncotarget 72 28423525
2022 Metformin suppresses the growth of colorectal cancer by targeting INHBA to inhibit TGF-β/PI3K/AKT signaling transduction. Cell death & disease 68 35236827
2022 CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner. Cell death & disease 66 35338119
2016 MiR-146a modulates macrophage polarization in systemic juvenile idiopathic arthritis by targeting INHBA. Molecular immunology 61 27541693
2009 INHBA overexpression promotes cell proliferation and may be epigenetically regulated in esophageal adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 56 19240652
2021 TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment. Molecular therapy : the journal of the American Society of Gene Therapy 50 33429081
2021 Inhibin β-A (INHBA) induces epithelial-mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway. Bioengineered 45 34346300
2017 Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens. JCI insight 40 28814667
2020 Preeclampsia-Associated lncRNA INHBA-AS1 Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells. Molecular therapy. Nucleic acids 34 33230466
2024 INHBA(+) cancer-associated fibroblasts generate an immunosuppressive tumor microenvironment in ovarian cancer. NPJ precision oncology 33 38360876
2021 INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN. The Journal of international medical research 29 34130530
2021 INHBA transfection regulates proliferation, apoptosis and hormone synthesis in sheep granulosa cells. Theriogenology 28 34537472
2023 Elevated expression of the RNA-binding protein IGF2BP1 enhances the mRNA stability of INHBA to promote the invasion and migration of esophageal squamous cancer cells. Experimental hematology & oncology 27 37644505
2019 Targeting INHBA in Ovarian Cancer Cells Suppresses Cancer Xenograft Growth by Attenuating Stromal Fibroblast Activation. Disease markers 27 31827640
2021 A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers. Oncogene 25 34239043
2021 INHBA is a novel mediator regulating cellular senescence and immune evasion in colorectal cancer. Journal of Cancer 21 34476008
2024 Discovery of PELATON links to the INHBA gene in the TGF-β pathway in colorectal cancer using a combination of bioinformatics and experimental investigations. International journal of biological macromolecules 19 38735606
2009 INHBA-associated markers as candidates for stallion fertility. Reproduction in domestic animals = Zuchthygiene 19 19144026
2024 INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling. Acta pharmacologica Sinica 16 39223366
2022 Upregulation of INHBA mediated by the transcription factor BHLHE40 promotes colon cancer cell proliferation and migration. Journal of clinical laboratory analysis 16 35689549
2019 Expression and gene regulation network of INHBA in Head and neck squamous cell carcinoma based on data mining. Scientific reports 15 31586103
2023 Impaired angiogenesis in diabetic critical limb ischemia is mediated by a miR-130b/INHBA signaling axis. JCI insight 14 37097749
2023 Identification of INHBA as a potential biomarker for gastric cancer through a comprehensive analysis. Scientific reports 14 37528145
2022 INHBA is a mediator of aggressive tumor behavior in HER2+ basal breast cancer. Breast cancer research : BCR 14 35248133
2020 INHBA knockdown inhibits proliferation and invasion of nasopharyngeal carcinoma SUNE1 cells in vitro. International journal of clinical and experimental pathology 14 32509056
2022 Comprehensive analysis of INHBA: A biomarker for anti-TGFβ treatment in head and neck cancer. Experimental biology and medicine (Maywood, N.J.) 13 35521936
2020 microRNA-211-mediated targeting of the INHBA-TGF-β axis suppresses prostate tumor formation and growth. Cancer gene therapy 13 33223523
2025 The YTHDF3-DT/miR-301a-3p /INHBA axis attenuates autophagy-dependent ferroptosis in lung adenocarcinoma. Cancer letters 12 39892700
2024 INHBA regulates Hippo signaling to confer 5-FU chemoresistance mediated by cellular senescence in colon cancer cells. The international journal of biochemistry & cell biology 10 38588888
2023 Integrated analysis of single cell and bulk RNA sequencing identifies CTHRC1+ INHBA+ CAF as drivers of colorectal cancer progression. Molecular carcinogenesis 10 37539967
2023 INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation. Journal of orthopaedic surgery and research 9 37940978
2022 BMSCs overexpressed ISL1 reduces the apoptosis of islet cells through ANLN carrying exosome, INHBA, and caffeine. Cellular and molecular life sciences : CMLS 9 36190571
2022 Exploration the role of INHBA in Hu sheep granulosa cells using RNA-Seq. Theriogenology 9 36525859
2020 A polymorphism in the cachexia-associated gene INHBA predicts efficacy of regorafenib in patients with refractory metastatic colorectal cancer. PloS one 9 32970737
2020 LncRNA INHBA-AS1 promotes colorectal cancer cell proliferation by sponging miR-422a to increase AKT1 axis. European review for medical and pharmacological sciences 9 33090398
2011 Coding regions of INHBA, SFRP4 and HOXA10 are not implicated in familial endometriosis linked to chromosome 7p13-15. Molecular human reproduction 9 21576276
2024 INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression. Cancer research communications 8 38329386
2024 Positive GLI1/INHBA feedback loop drives tumor progression in gastric cancer. Cancer science 8 38676428
2024 FAP+ gastric cancer mesenchymal stromal cells via paracrining INHBA and remodeling ECM promote tumor progression. International immunopharmacology 8 39615112
2022 Extracellular vesicles extracted from bone marrow mesenchymal stem cells carrying MicroRNA-342-3p inhibit the INHBA/IL13Rα2 axis to suppress the growth and metastasis of breast cancer. Translational oncology 8 35093789
2020 LncRNA INHBA-AS1 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by sponging miR-143-3p. European review for medical and pharmacological sciences 8 32141551
2024 Elevated INHBA Promotes Tumor Progression of Cervical Cancer. Technology in cancer research & treatment 7 38419562
2022 DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma. International journal of molecular sciences 7 35216189
2021 An immune-related model based on INHBA, JAG2 and CCL19 to predict the prognoses of colon cancer patients. Cancer cell international 7 34103052
2025 INHBA+ macrophages and Pro-inflammatory CAFs are associated with distinctive immunosuppressive tumor microenvironment in submucous Fibrosis-Derived oral squamous cell carcinoma. BMC cancer 6 40355814
2024 miR-134-3p Regulates Cell Proliferation and Apoptosis by Targeting INHBA via Inhibiting the TGF-β/PI3K/AKT Pathway in Sheep Granulosa Cells. Biology 6 39857255
2021 Silencing of long noncoding INHBA antisense RNA1 suppresses proliferation, migration, and extracellular matrix deposition in human hypertrophic scar fibroblasts via regulating microRNA-141-3p/myeloid cell leukemia 1 axis. Bioengineered 6 33977869
2023 MiR-29c-5p regulates the function of buffalo granulosa cells to induce follicular atresia by targeting INHBA. Theriogenology 5 37086585
2023 The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer. Frontiers in bioscience (Landmark edition) 5 38062804
2021 Effect of Mouse Ovarian Vitrification on Promoter Methylation of Inhba and Inhbb in Granulosa Cells of Follicles. Cryo letters 5 33970982
2013 Changes in the reproductive endocrine function in rat following intraovary microinjection of inhba overexpression lentivirus vectors. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 5 23767829
2000 Linkage mapping of the ovine alpha-inhibin (INHA) beta(A)-inhibin/activin (INHBA) and beta(B)-inhibin/activin (INHBB) genes. The Journal of heredity 4 10912684
2025 INHBA, transcriptionally activated by SPI1, facilitates gastric cancer progression by inducing macrophage recruitment and M2 polarization via activating the TGF-β signaling to increase CCL2. Pathology, research and practice 3 40132395
2025 INHBA knockdown inhibits renal fibrosis in mice following ischemia-reperfusion injury by suppressing activation of the TGF-β/Smad signaling pathway. BMC nephrology 3 41013408
2022 Dysregulation of Npas4 and Inhba expression and an altered excitation-inhibition balance are associated with cognitive deficits in DBA/2 mice. Learning & memory (Cold Spring Harbor, N.Y.) 3 35042829
2024 COL10A1 Facilitates Prostate Cancer Progression by Interacting With INHBA to Activate the PI3K/AKT Pathway. Journal of cellular and molecular medicine 2 39656597
2026 INHBA, regulated by C/EBPβ, induces M2 macrophage polarization to promote tumor metastasis and growth via activating the PI3K/AKT pathway in gastric cancer. British journal of cancer 0 41540191
2026 INHBA Promotes the Progression of Gastric Cancer by Activating MAPK Signaling Pathway via Targeting ITGA6. Oncology research 0 41799510
2026 THBS2 Promotes Prostate Cancer Malignancy via INHBA-Dependent FAK/PI3K/AKT Signaling Activation. Analytical cellular pathology (Amsterdam) 0 41810913
2025 INHBA: A Protein-coding Gene Closely Related to Tumour Diseases. Current topics in medicinal chemistry 0 40754873
2025 Spatial transcriptomics reveals Inhba/Smad2/E2f4 axis in Lrp2high thecal cell proliferation in androgen-induced PCOS mice. Frontiers in cell and developmental biology 0 40831751
2025 Rhapontigenin inhibits inflammation and senescence of chondrocytes from patients with osteoarthritis by targeting INHBA. International immunopharmacology 0 41218586
2025 INHBA promotes chemoresistance in pancreatic cancer by enhancing CTPS1 stability and mediating pyrimidine metabolism. Cancer cell international 0 41239468
2025 Machine learning identifies INHBA DPT ADH7 FBP2 and GPR155 as diagnostic biomarkers for gastric cancer. Discover oncology 0 41326944
2025 Inhba, Homer1 and Bdnf are major targets of transcriptomic dysregulation by neurodegenerative disease-associated excitotoxic NMDA receptor signaling. Communications biology 0 41339520
2025 Targeting KAT8 alleviates vascular senescence by modulating the INHBA/TGF-β pathway. Molecular therapy : the journal of the American Society of Gene Therapy 0 41445196
2023 Pharmacological investigation of vitamin E with combined oral contraceptives on INHBA gene against PCOS that intricate through melatonin PKC pathway. Systems biology in reproductive medicine 0 37962399
2020 LncRNA INHBA-AS1 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by sponging miR-143-3p. European review for medical and pharmacological sciences 0 33015761