Affinage

INHBA

Inhibin beta A chain · UniProt P08476

Length
426 aa
Mass
47.4 kDa
Annotated
2026-06-10
77 papers in source corpus 31 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INHBA encodes the inhibin β-A subunit that dimerizes to form the secreted TGF-β superfamily ligand activin A, a paracrine signaling factor whose activities span tumor microenvironment remodeling, immune modulation, neuroprotection, and reproductive endocrinology (PMID:26279570, PMID:38360876, PMID:39223366, PMID:34537472). Across diverse cancers, secreted INHBA/activin A engages SMAD2/3 signaling to activate cancer-associated fibroblasts and drive collagen/ECM deposition, proliferation, migration, and invasion (PMID:28814667, PMID:31827640, PMID:39615112); INHBA-positive CAFs induce PD-L1 in a SMAD2-dependent autocrine loop and promote regulatory T cell differentiation, while tumor-intrinsic INHBA suppresses IFN-γ signaling to reduce CXCL9/CXCL10-driven effector T cell infiltration—effects reversed by activin A neutralizing antibodies (PMID:38360876, PMID:39223366). INHBA further promotes macrophage M2 polarization, in part through SMAD2/TGF-β-driven CCL2 induction, integrating it into a broader immunosuppressive program (PMID:27541693, PMID:40132395, PMID:41540191). Beyond classical SMAD signaling, INHBA acts through physical partners: it interacts with integrin ITGA6 to activate MAPK signaling, with CTPS1 to block SMURF1-mediated ubiquitination and stabilize pyrimidine metabolism for gemcitabine resistance, and serves as a required downstream mediator of COL10A1- and THBS2-driven PI3K/AKT signaling (PMID:41239468, PMID:41799510, PMID:39656597, PMID:41810913). INHBA expression is tightly controlled transcriptionally by SPI1, C/EBPβ, GLI1, BHLHE40 and KAT8-dependent epigenetics, and post-transcriptionally by miRNAs (miR-146a, miR-130b-3p, miR-204-5p) and the m6A reader IGF2BP1/HuR axis (PMID:27541693, PMID:35338119, PMID:37644505, PMID:37097749, PMID:41445196, PMID:38676428, PMID:35689549, PMID:40132395, PMID:41540191). In the nervous system, a BDNF→synaptic NMDAR→nuclear calcium axis upregulates Inhba, and the resulting activin A dampens extrasynaptic NMDAR-mediated calcium influx to confer neuroprotection against excitotoxicity and ischemic damage [#1 corrected to #1, #1]. In the brain, this neuroprotective role is established by (PMID:26279570) (developmental compensation) and the BDNF-driven axis (PMID:26279570).

Mechanistic history

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

    Established that the inhibin β-A subunit has distinct, non-redundant in vivo functions whose appropriate spatiotemporal expression—not just protein identity—determines developmental outcomes, by testing whether the β-B subunit could functionally substitute.

    Evidence Targeted knock-in replacing the Inhba mature coding region with Inhbb in mice, with phenotypic rescue analysis

    PMID:10932194

    Open questions at the time
    • Does not define the molecular receptor/effector differences between β-A and β-B
    • Does not address adult/cancer functions
  2. 2009 Medium

    First linked INHBA/activin A to oncogenic proliferation and showed its expression is epigenetically controlled, framing INHBA as a tumor-promoting secreted factor.

    Evidence siRNA knockdown, recombinant activin A, follistatin inhibition, and DNA-methylation/HDAC inhibitor treatment in esophageal adenocarcinoma cell lines

    PMID:19240652

    Open questions at the time
    • No in vivo validation
    • Downstream signaling pathway not defined
    • Specific promoter regulatory elements not mapped
  3. 2015 High

    Defined a neuroprotective signaling axis, showing activity-dependent Inhba induction restrains pathological extrasynaptic NMDAR signaling.

    Evidence Calcium imaging, synaptic/extrasynaptic NMDAR pharmacology, inhba siRNA, recombinant activin A, and an in vivo mouse stroke model

    PMID:26279570

    Open questions at the time
    • Receptor/effector mechanism by which activin A reduces extrasynaptic NMDAR flux not resolved
    • Human relevance not established
  4. 2016 High

    Placed INHBA as a functional downstream node of miR-146a controlling macrophage polarization, connecting INHBA to immune-cell programming.

    Evidence 3'-UTR luciferase reporter, miRNA gain/loss-of-function, and INHBA rescue with macrophage polarization markers and cytokine readouts

    PMID:27541693

    Open questions at the time
    • Does not define how INHBA signals into macrophages
    • In vivo confirmation absent
  5. 2017 High

    Identified INHBA as a paracrine driver of CAF activation downstream of adrenergic stress signaling, defining its role in tumor stroma remodeling.

    Evidence Restraint-stress in vivo cancer models, β-blocker pharmacology, INHBA shRNA/siRNA, and CAF/collagen marker imaging

    PMID:28814667

    Open questions at the time
    • Receptor on fibroblasts not identified here
    • Downstream SMAD requirement defined in later work
  6. 2019 Medium

    Demonstrated INHBA-driven stromal activation and tumor growth require SMAD2 and that INHBA sustains active TGF-β signaling in cancer cells.

    Evidence INHBA shRNA in ovarian and gastric cancer cells, Smad2 inhibition, xenografts, and TGF-β pathway Western blots

    PMID:30963572 PMID:31827640

    Open questions at the time
    • Single-lab studies
    • Receptor complex engaged not directly identified
  7. 2021 High

    Expanded INHBA's immunomodulatory mechanism, showing INHBA+ CAFs induce PD-L1 via autocrine SMAD2 and drive Treg differentiation, with activin A neutralization as a therapeutic strategy.

    Evidence INHBA knockdown in ovarian CAFs, CAF/T cell co-culture, recombinant activin A, and anti-activin A neutralizing antibody in vivo with patient tissue analysis

    PMID:38360876

    Open questions at the time
    • Direct contact molecule mediating Treg differentiation not identified
    • Generality across tumor types not tested here
  8. 2021 Medium

    Connected INHBA to therapy resistance and metabolic reprogramming, showing stromal- and tumor-intrinsic INHBA supports glycolysis and lapatinib resistance in HER2+ breast cancer.

    Evidence siRNA knockdown, metabolic profiling, lapatinib sensitivity assays, and PEAK1-dependent conditioned-medium secretome analysis in MSCs/CAFs

    PMID:34239043 PMID:35248133

    Open questions at the time
    • Direct molecular link between INHBA and metabolic switch not defined
    • Single-lab studies
  9. 2021 Medium

    Established INHBA as a regulator of ovarian granulosa cell steroidogenesis and follicular hormone output.

    Evidence INHBA overexpression/knockdown in sheep granulosa cells with hormone ELISA and TGF-β gene expression analysis

    PMID:34537472

    Open questions at the time
    • Mechanism of steroidogenic gene control not defined
    • Single species, in vitro
  10. 2022 Medium

    Defined multiple post-transcriptional and transcriptional control layers (circTHBS1/miR-204-5p/HuR, BHLHE40) and pharmacological suppression (metformin) governing INHBA-driven TGF-β/PI3K-Akt and Hippo signaling.

    Evidence RNA pulldown, RIP, luciferase reporters, metformin treatment, cell-cycle/senescence assays, and Verteporfin Hippo inhibition across colon and gastric cancer models

    PMID:35236827 PMID:35338119 PMID:35689549 PMID:38588888

    Open questions at the time
    • BHLHE40 regulation lacks direct ChIP
    • Causal hierarchy among co-regulated pathways not resolved
  11. 2023 High

    Established m6A-dependent stabilization of INHBA mRNA by IGF2BP1 and microRNA control of an INHBA-angiogenesis axis, linking RNA regulation to downstream Smad2/3 and IL-8 signaling.

    Evidence RIP-seq, RNA pulldown, m6A PCR, RNA stability assays, BTYNB inhibitor (IGF2BP1), and miR-130b-3p mimics/inhibitors with INHBA siRNA epistasis in endothelial cells and in vivo ischemia models

    PMID:37097749 PMID:37644505

    Open questions at the time
    • Receptor-level events downstream of activin A in endothelium not fully mapped
    • Cross-talk between BMP and TGF-β arms not dissected
  12. 2024 Medium

    Revealed INHBA's direct physical partners and non-SMAD effector routes—ITGA6/MAPK, CTPS1 stabilization for pyrimidine metabolism, and IFN-γ pathway suppression—broadening its mechanism beyond canonical ligand signaling.

    Evidence Co-IP/Co-IF (ITGA6), IP-MS and ubiquitination assays (CTPS1), and gain/loss-of-function with anti-activin A antibody (garetosmab) plus anti-PD-L1 across multiple mouse tumor models

    PMID:39223366 PMID:41239468 PMID:41799510

    Open questions at the time
    • Whether intracellular CTPS1 binding reflects non-secreted INHBA pool not resolved
    • Structural basis of partner interactions unknown
  13. 2024 Medium

    Mapped transcriptional regulators (GLI1 feedback loop, KAT8 epigenetic axis, SPI1) and paracrine FAP+ stromal sources controlling INHBA in cancer and vascular senescence.

    Evidence ChIP and reporter assays (GLI1, SPI1), CRISPR multi-omics (KAT8), and FAP+ cell isolation with ELISA/SMAD2/3 readouts

    PMID:38676428 PMID:39615112 PMID:40132395 PMID:41445196

    Open questions at the time
    • Relative contribution of each regulator in physiological tissue unknown
    • Single-lab studies
  14. 2025 Medium

    Reinforced INHBA's neuroprotective and reproductive roles, identifying its suppression in neurodegeneration and its function in thecal cell proliferation in PCOS.

    Evidence esNMDAR activation with RNA-seq and Huntington's disease mouse model rescue (memantine/FP802); spatial transcriptomics with Inhba/Smad2/E2f4 knockdown in a PCOS mouse model

    PMID:40831751 PMID:41339520

    Open questions at the time
    • Mechanism connecting esNMDAR to Inhba transcriptional repression not detailed
    • Human relevance of PCOS axis not established
  15. 2026 Medium

    Identified additional INHBA-dependent oncogenic signaling partners (COL10A1, THBS2 via FAK/PI3K/AKT) and a role in valvular osteogenic calcification, extending its mechanistic reach.

    Evidence Co-IP and INHBA-knockdown rescue with PI3K/AKT/FAK readouts in prostate cancer; INHBA siRNA with osteogenic induction and single-cell RNA-seq in valvular interstitial cells

    PMID:39656597 PMID:41810913 PMID:42059080

    Open questions at the time
    • THBS2-INHBA interaction inferred without direct Co-IP
    • Mechanism of INHBA in calcification not molecularly defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor complexes and structural determinants linking secreted activin A versus intracellular INHBA interactions (CTPS1, integrins, collagens) to the divergent SMAD, MAPK, and PI3K/AKT outputs remain undefined, as does how a single ligand selects among context-specific effector programs.
  • No structural model of INHBA-partner complexes
  • Receptor selection mechanism across tissues unknown
  • Distinction between secreted ligand and intracellular binding pools unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 2 R-HSA-1266738 Developmental Biology 1
Partners
COL10A1CTPS1IGF2BP1ITGA6SMURF1THBS2

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Replacement of the Inhba mature-protein coding region with Inhbb (creating the InhbaBK knock-in allele) rescued the craniofacial/palate/tooth phenotypes of Inhba-null mice but produced novel somatic, testicular, genital, and hair-growth phenotypes, demonstrating that functional compensation within the TGF-β superfamily depends on appropriate spatiotemporal expression and that Inhba and Inhbb have overlapping but non-identical in vivo activities. Gene knock-in / targeted replacement (Inhba locus replaced with Inhbb coding sequence), in vivo mouse genetics, phenotypic rescue analysis Nature genetics High 10932194
2015 BDNF activates synaptic NMDA receptors, triggering nuclear calcium signaling that transcriptionally upregulates inhba (inhibin β-A/activin A homodimer). The resulting activin A then reduces extrasynaptic NMDA-receptor-mediated calcium influx, thereby protecting neurons against mitochondrial dysfunction and excitotoxicity. This BDNF → synaptic NMDAR → nuclear calcium → Inhba → reduced extrasynaptic NMDAR signaling axis confers neuroprotection against ischemic brain damage in a mouse stroke model. Primary neuron live-cell calcium imaging, pharmacological block of synaptic vs. extrasynaptic NMDARs, siRNA knockdown of inhba, recombinant activin A application, in vivo mouse stroke model, nuclear calcium reporters Cell reports High 26279570
2009 INHBA overexpression in esophageal adenocarcinoma (EAC) cell lines promotes cell proliferation; exogenous activin A increases proliferation of FLO and OE-33 cells, while follistatin (activin inhibitor) and INHBA-targeting siRNA reduce proliferation. INHBA expression in EAC cell lines is upregulated by treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine and the HDAC inhibitor trichostatin A, indicating that promoter demethylation and histone acetylation regulate INHBA expression. siRNA knockdown, exogenous recombinant activin A treatment, follistatin inhibitor treatment, 5-AZA and trichostatin A epigenetic drug treatment, cell proliferation assays, real-time RT-PCR, IHC Journal of thoracic oncology Medium 19240652
2017 Cancer-cell-derived INHBA (inhibin β-A/activin A) induces cancer-associated fibroblast (CAF) activation in ovarian cancer models. Adrenergic (stress) signaling increases INHBA production by cancer cells; ablating INHBA expression decreases CAF phenotype and associated collagen/ECM deposition both in vitro and in vivo. This identifies INHBA as a paracrine driver of the CAF phenotype downstream of adrenergic signaling. In vivo restraint-stress mouse models of ovarian/breast/colon cancer, β-blocker pharmacology, bioinformatics-guided systems biology, siRNA/shRNA ablation of INHBA in vitro and in vivo, immunofluorescence/IHC for CAF markers and collagens JCI insight High 28814667
2016 miR-146a directly targets the 3'-UTR of INHBA to suppress its expression. INHBA mediates macrophage M1/M2 polarization: INHBA overexpression rescues M1 cytokine production (IL-6, IL-12, TNF-α) suppressed by miR-146a, and rescues M2 markers (Arg1, CCL17, CCL22) suppressed by miR-146a inhibition. Thus miR-146a regulates monocyte polarization through INHBA. 3'-UTR luciferase reporter assay, miRNA overexpression/knockdown, INHBA overexpression/knockdown rescue experiments, cytokine measurement, flow cytometry for macrophage polarization markers Molecular immunology High 27541693
2019 INHBA knockdown in ovarian cancer cells impairs xenograft tumor growth in vivo by reducing stromal fibroblast activation. Mechanistically, INHBA-induced stromal fibroblast activation depends on Smad2 signaling; inhibiting Smad2 pathway reverses INHBA-driven fibroblast activation. shRNA knockdown of INHBA in OC cells, xenograft mouse model, Smad2 pathway inhibition, in vitro co-culture fibroblast activation assays Disease markers Medium 31827640
2019 INHBA gene silencing via shRNA inhibits TGF-β signaling pathway activation in gastric cancer cells, reducing cell migration, invasion, proliferation, and tumor growth in a xenograft nude mouse model. Conversely, INHBA is required to maintain active TGF-β signaling in GC cells. shRNA knockdown of INHBA, Western blot for TGF-β pathway proteins, migration/invasion/proliferation assays, xenograft tumor model in nude mice Journal of cellular physiology Medium 30963572
2021 INHBA in ovarian CAFs induces PD-L1 expression in an autocrine manner through SMAD2-dependent signaling, and INHBA+ CAFs promote regulatory T cell (Treg) differentiation via direct cell contact. Neutralizing Activin A (INHBA homodimer) antibody in vivo attenuates tumor progression and reduces pro-tumorigenic myofibroblasts and macrophages. INHBA knockdown in human ovarian CAFs, T cell/CAF co-culture assay for Treg differentiation, recombinant Activin A treatment, anti-Activin A neutralizing antibody in vivo in mouse ovarian cancer models, SMAD2 pathway analysis, spatiotemporal patient tissue analysis NPJ precision oncology High 38360876
2021 INHBA promotes colon cancer cell proliferation, migration, and invasion through upregulation of versican (VCAN). The INHBA-VCAN correlation was verified by immunoprecipitation, and INHBA interference inhibited aggressive behavior by downregulating VCAN. Immunoprecipitation, siRNA knockdown of INHBA and VCAN, overexpression, CCK-8/colony formation, wound healing, Transwell assays The Journal of international medical research Low 34130530
2021 In HER2+ basal breast cancer cells, INHBA knockdown slows growth, increases lapatinib sensitivity, and shifts cellular metabolism from glycolysis to oxidative phosphorylation, indicating INHBA supports a glycolytic and invasive phenotype in the basal subtype. siRNA knockdown screen, 2D and 3D cell culture validation, metabolic profiling, lapatinib sensitivity assays Breast cancer research : BCR Medium 35248133
2021 MSC-derived INHBA/activin-A is a necessary paracrine factor mediating lapatinib resistance of HER2+ breast cancer cells in a PEAK1-dependent stromal axis (SNAI2-PEAK1-INHBA). INHBA in conditioned media from PEAK1-expressing MSCs promotes lapatinib resistance, as established by analysis of PEAK1-dependent secreted factors. Conditioned medium transfer experiments, PEAK1 knockdown/overexpression in MSCs and CAFs, secretome analysis, single-cell cyclic immunofluorescence (CycIF), co-culture systems Oncogene Medium 34239043
2022 Metformin suppresses CRC cell proliferation causing G1/S arrest by downregulating INHBA expression, which blocks TGF-β signaling activation and downstream PI3K/Akt pathway activity, leading to reduced cyclin D1. INHBA knockdown and overexpression in CRC cells, metformin treatment, cell cycle analysis (flow cytometry), Western blot for TGF-β/PI3K/Akt pathway components, proliferation assays Cell death & disease Medium 35236827
2022 CircTHBS1 promotes INHBA expression via two mechanisms: (1) sponging miR-204-5p to relieve repression of INHBA mRNA, and (2) enhancing HuR-mediated mRNA stability of INHBA. Elevated INHBA consequently activates the TGF-β pathway to drive gastric cancer malignancy. RNA pulldown, luciferase reporter assay, RNA immunoprecipitation (RIP), gain/loss-of-function assays in vitro and in vivo, transcriptome analysis Cell death & disease Medium 35338119
2023 RNA-binding protein IGF2BP1 binds and stabilizes INHBA mRNA (via m6A-dependent mechanism), leading to higher INHBA protein expression and activation of Smad2/3 signaling, which promotes invasion and migration of esophageal squamous cancer cells. IGF2BP1 also interacts with G3BP1, and G3BP1 knockdown similarly downregulates INHBA-Smad2/3 signaling. RNA immunoprecipitation sequencing (RIP-seq), RNA pulldown, gene-specific m6A PCR, RNA stability assays, immunofluorescence, mass spectrometry, siRNA knockdown, in vivo metastasis assays, small-molecule inhibitor BTYNB Experimental hematology & oncology High 37644505
2023 miR-130b-3p directly targets and represses INHBA mRNA. INHBA repression (either by miR-130b overexpression or INHBA siRNA) induces IL-8 expression, a pro-angiogenic chemokine, and improves revascularization in diabetic ischemic limbs in vivo. Thus a miR-130b/INHBA axis controls angiogenesis by modulating BMP/TGF-β signaling in endothelial cells. miRNA target prediction with experimental validation, miRNA mimic/inhibitor transfection in endothelial cells, siRNA knockdown of INHBA, in vitro angiogenic assays (proliferation, migration, sprouting), in vivo femoral artery ligation in diabetic (db/db) mice, RNA-seq/GSEA JCI insight High 37097749
2024 Tumor-intrinsic INHBA suppresses the IFN-γ signaling pathway, leading to (1) reduced IFN-γ-induced PD-L1 expression (causing poor response to anti-PD-L1 therapy) and (2) decreased secretion of IFN-γ-stimulated chemokines CXCL9 and CXCL10, impairing effector T cell infiltration into tumors. Activin A-specific antibody garetosmab improves anti-tumor immunity and synergizes with anti-PD-L1 antibody atezolizumab. INHBA gain/loss-of-function in CT26, MC38, B16, and 4T1 mouse tumor models, anti-PD-L1 antibody treatment, anti-Activin A antibody (garetosmab) treatment, flow cytometry for T cell infiltration, IFN-γ signaling pathway analysis, cytokine/chemokine measurement Acta pharmacologica Sinica High 39223366
2024 KAT8 (lysine acetyltransferase 8) suppresses vascular senescence by epigenetically regulating the INHBA/TGF-β/P15 signaling axis. KAT8 deficiency increases INHBA expression, promoting TGF-β-mediated senescence, while KAT8 overexpression attenuates vascular senescence. hsa-miR-339-3p is identified as responsible for age-related KAT8 downregulation upstream of this axis. CRISPR-Cas9 loss-of-function and gain-of-function in endothelial cells and mice (C57BL/6J and ApoE-/-), integrated miRNA-seq/ATAC-seq/RNA-seq multi-omics analysis, senescence assays Molecular therapy Medium 41445196
2024 GLI1 (Hedgehog transcription factor) transcriptionally upregulates INHBA in gastric cancer. Elevated INHBA in turn activates Smads signaling, which transcriptionally activates GLI1, forming a positive GLI1/INHBA feedback loop that drives GC tumorigenesis. Additionally, H. pylori upregulates GLI1 via m6A modification through the FTO/YTHDF2/GLI1 pathway, feeding into this loop. Chromatin immunoprecipitation, reporter assays, gain/loss-of-function for GLI1 and INHBA, in vivo mouse tumor models disrupting GLI1-INHBA interaction, m6A modification analysis Cancer science Medium 38676428
2024 INHBA promotes chemoresistance in pancreatic cancer by physically interacting with CTPS1 (cytidine triphosphate synthase 1) and competitively inhibiting SMURF1-mediated ubiquitination of CTPS1, thereby stabilizing CTPS1 protein and enhancing pyrimidine metabolism that supports gemcitabine resistance. Immunoprecipitation mass spectrometry (to identify CTPS1 as binding partner), co-immunoprecipitation, ubiquitination assays, drug sensitivity analysis, xenograft mouse model, EdU/flow cytometry/colony formation assays Cancer cell international Medium 41239468
2024 FAP+ gastric cancer mesenchymal stromal cells secrete INHBA via paracrine signaling to activate SMAD2/3 signaling in gastric cancer cells, increasing their proliferation and migration. These cells also induce collagen deposition that acts via integrin ITGB1 to phosphorylate FAK and YAP, promoting invasion and stemness. FAP+ cell isolation by flow cytometry, conditioned medium/ELISA experiments, Western blot for SMAD2/3, Masson's trichrome staining, IHC, transcriptomic sequencing International immunopharmacology Medium 39615112
2024 INHBA promotes gastric cancer progression by interacting with ITGA6 (integrin alpha-6) to activate the MAPK signaling pathway. Co-immunoprecipitation and co-immunofluorescence confirmed the INHBA-ITGA6 interaction; rescue experiments demonstrated that ITGA6 mediates INHBA-driven MAPK activation, proliferation, migration, and invasion. Co-immunoprecipitation (Co-IP), co-immunofluorescence, RNA-seq pathway analysis, Western blot, rescue experiments with ITGA6 manipulation, in vivo xenograft models, RT-qPCR, IHC Oncology research Medium 41799510
2022 INHBA confers 5-FU chemoresistance in colon cancer by promoting cellular senescence and inactivating the Hippo signaling pathway (as validated using the Hippo pathway inhibitor Verteporfin). INHBA knockdown enhanced 5-FU sensitivity, inhibited proliferation, promoted apoptosis, and reduced senescent cell proportion and senescence markers (IL-6, IL-8). INHBA knockdown/overexpression, 5-FU drug sensitivity assays, cellular senescence assays (SA-β-gal, senescence marker expression), Verteporfin (Hippo inhibitor) treatment, in vivo xenograft model, flow cytometry for cell cycle The international journal of biochemistry & cell biology Medium 38588888
2025 Extrasynaptic NMDA receptor (esNMDAR) activation suppresses Inhba transcription in hippocampal neurons as part of a broad neurodegenerative transcriptional dysregulation program. In a Huntington's disease mouse model, treatment with memantine or FP802 (NMDAR/TRPM4 complex inhibitor) restores Inhba expression along with Bdnf and Homer1, attenuating disease progression markers. Inhba is identified as a major neuroprotective gene whose suppression contributes to neurodegeneration. Primary hippocampal neuron cultures with pharmacological esNMDAR activation, RNA-seq, Huntington's disease mouse model (memantine and FP802 treatment), quantitative gene expression analysis Communications biology Medium 41339520
2021 INHBA transfection in sheep granulosa cells: overexpression significantly decreases activin A and estradiol secretion while increasing inhibin A and progesterone secretion. INHBA overexpression also decreased FSH-β subunit expression. INHBA knockdown inhibited expression of multiple TGF-β-related genes. These results establish INHBA as a regulator of granulosa cell hormone synthesis and follicular development. In vitro transfection (overexpression and siRNA knockdown) in sheep granulosa cells, hormone ELISA, RT-qPCR/Western blot for cell cycle and apoptosis genes, proliferation assays Theriogenology Medium 34537472
2025 Spatial transcriptomics in a PCOS mouse model identified an Inhba/Smad2/E2f4 signaling axis as a key regulator of Lrp2-high thecal cell proliferation. Knockdown of any component of this axis (Inhba, Smad2, or E2f4) significantly suppressed thecal cell proliferation in vitro, with the greatest effect from Inhba silencing. This axis is implicated in androgen excess in PCOS. Spatial transcriptomics, siRNA knockdown of Inhba/Smad2/E2f4, EdU incorporation assay, flow cytometry for cell cycle, DHEA-induced PCOS mouse model Frontiers in cell and developmental biology Medium 40831751
2025 In a preprint, integrin α2 (Itgα2) engagement with collagen I induces INHBA expression in basal-like breast cancer cells, activating TGF-β signaling which upregulates vimentin while preserving epithelial junction gene expression, thus driving a partial EMT (leader cell phenotype) that enables collective invasion. Itgα2 also promotes ECM degradation through a TGF-β-independent mechanism. Collagen I-responsive cell subset identification, Itgα2 perturbation, INHBA expression analysis, TGF-β signaling readouts, vimentin and E-cadherin/junction gene quantification, in vitro collective invasion assays bioRxivpreprint Low
2025 In a preprint, TRIM71 represses Inhba (and Tgfbr2) expression in cochlear progenitor cells. Loss of TRIM71 function leads to premature hair cell differentiation; analysis of Inhba;Tgfbr1 double knockout mice indicates TRIM71 maintains hair cell progenitors in a proliferative undifferentiated state by restricting TGF-β-type signaling, placing Inhba downstream of TRIM71 in this developmental pathway. Conditional Trim71 knockout mice, Inhba;Tgfbr1 double knockout mice, transcriptomic profiling of cochlear progenitors, in vivo developmental timing analysis bioRxivpreprint Low
2025 In a preprint, mesenchyme-specific deletion of Gata2 reduces Inhba expression in the epididymal mesenchyme and impairs epithelial proliferation and epididymal coiling. This identifies Inhba as downstream of GATA2 in androgen-independent mesenchymal signaling required for epididymal development. Conditional mesenchyme-specific Gata2 knockout mice, dihydrotestosterone supplementation rescue experiments, Inhba expression analysis by RT-qPCR/IHC, epithelial proliferation assays bioRxivpreprint Low
2025 In JunB-deficient Th17 cells, Inhba (encoding activin A) is identified as a JunB transcriptional target. Supplementation with recombinant activin A restores IL-17A and Rorc expression during pathogenic Th17 cell differentiation in JunB-deficient conditions, establishing activin A as a functional downstream effector of JunB-driven Th17 differentiation. dTAG protein degradation of JunB in Th17 cells, transcriptomic analysis, recombinant activin A rescue, flow cytometry for IL-17A and RORγt, in vitro and in vivo Th17 differentiation bioRxivpreprint Low
2022 INHBA transcription in colon cancer cells is directly activated by the transcription factor BHLHE40, as established through database analysis and experimental validation showing BHLHE40 modulates INHBA expression; BHLHE40 knockdown suppresses INHBA and reduces colon cancer cell proliferation and migration. siRNA knockdown of BHLHE40, Western blot and RT-qPCR, database analysis (JASPAR, PROMO, ENCODE), CCK-8 proliferation and wound healing assays Journal of clinical laboratory analysis Low 35689549
2025 SPI1 (PU.1) transcription factor binds to the INHBA promoter and transcriptionally activates INHBA expression in gastric cancer cells. INHBA in turn activates TGF-β signaling to upregulate CCL2, which promotes macrophage recruitment and M2 polarization, facilitating GC cell proliferation, migration, and invasion. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), Western blot for TGF-β pathway, macrophage recruitment assays, co-culture experiments, in vivo xenograft model Pathology, research and practice Medium 40132395
2026 COL10A1 directly interacts with INHBA (co-immunoprecipitation) and facilitates PI3K/AKT pathway phosphorylation in prostate cancer cells and mouse models. INHBA knockdown reverses the oncogenic effects of COL10A1 overexpression, establishing INHBA as a required downstream mediator of COL10A1-driven PI3K/AKT signaling and PCa progression. Co-immunoprecipitation (Co-IP), Western blot for PI3K/AKT phosphorylation, siRNA knockdown of INHBA (rescue experiment), CCK-8, colony formation, flow cytometry, Transwell, wound-healing assays, mouse models Journal of cellular and molecular medicine Medium 39656597
2026 THBS2 directly interacts with INHBA to activate the FAK/PI3K/AKT signaling pathway in prostate cancer. INHBA knockdown reverses the oncogenic effects of THBS2 overexpression, demonstrating epistatic dependence of THBS2-driven signaling on INHBA. STRING interaction prediction, Western blot for FAK/PI3K/AKT phosphorylation, INHBA knockdown rescue experiments, overexpression/knockdown functional assays (CCK-8, invasion, EMT markers) Analytical cellular pathology (Amsterdam) Low 41810913
2026 C/EBPβ transcriptionally upregulates INHBA in gastric cancer cells (validated by dual-luciferase reporter and ChIP). INHBA then induces M2 macrophage polarization and activates a PI3K/AKT/TGF-β positive feedback loop, promoting tumor metastasis and growth. Dual-luciferase reporter assay, ChIP, INHBA gain/loss-of-function, macrophage polarization co-culture assays (CIBERSORT), in vitro/in vivo tumor models British journal of cancer Medium 41540191
2026 INHBA silencing in valvular interstitial cells (VICs) reduces osteogenic calcification in vitro; INHBA expression increases during osteogenic induction alongside RUNX2 and ALP. In vivo, INHBA expression differs across fetal, healthy, and calcified valve conditions, implicating INHBA in osteogenic remodeling of VICs in calcific aortic valve disease. siRNA knockdown of INHBA in VICs, osteogenic induction in vitro, ALP and RUNX2 expression measurement, single-cell RNA-seq of human valve tissue, GWAS/bulk RNA-seq integration Arteriosclerosis, thrombosis, and vascular biology Medium 42059080

Source papers

Stage 0 corpus · 77 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 130 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 57 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 52 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 37 33230466
2024 INHBA(+) cancer-associated fibroblasts generate an immunosuppressive tumor microenvironment in ovarian cancer. NPJ precision oncology 35 38360876
2021 INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN. The Journal of international medical research 30 34130530
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 28 37644505
2021 INHBA transfection regulates proliferation, apoptosis and hormone synthesis in sheep granulosa cells. Theriogenology 28 34537472
2019 Targeting INHBA in Ovarian Cancer Cells Suppresses Cancer Xenograft Growth by Attenuating Stromal Fibroblast Activation. Disease markers 28 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 26 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 18 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
2025 The YTHDF3-DT/miR-301a-3p /INHBA axis attenuates autophagy-dependent ferroptosis in lung adenocarcinoma. Cancer letters 14 39892700
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
2023 Integrated analysis of single cell and bulk RNA sequencing identifies CTHRC1+ INHBA+ CAF as drivers of colorectal cancer progression. Molecular carcinogenesis 12 37539967
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
2025 INHBA+ macrophages and Pro-inflammatory CAFs are associated with distinctive immunosuppressive tumor microenvironment in submucous Fibrosis-Derived oral squamous cell carcinoma. BMC cancer 9 40355814
2024 FAP+ gastric cancer mesenchymal stromal cells via paracrining INHBA and remodeling ECM promote tumor progression. International immunopharmacology 9 39615112
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 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 9 35093789
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
2022 DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma. International journal of molecular sciences 8 35216189
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
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 7 33977869
2021 An immune-related model based on INHBA, JAG2 and CCL19 to predict the prognoses of colon cancer patients. Cancer cell international 7 34103052
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
2023 The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer. Frontiers in bioscience (Landmark edition) 6 38062804
2023 MiR-29c-5p regulates the function of buffalo granulosa cells to induce follicular atresia by targeting INHBA. Theriogenology 5 37086585
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
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 4 40132395
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 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
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 2 41540191
2024 COL10A1 Facilitates Prostate Cancer Progression by Interacting With INHBA to Activate the PI3K/AKT Pathway. Journal of cellular and molecular medicine 2 39656597
2025 Targeting KAT8 alleviates vascular senescence by modulating the INHBA/TGF-β pathway. Molecular therapy : the journal of the American Society of Gene Therapy 1 41445196
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
2026 Multiomics Analysis Reveals Stromal Cell State Changes and INHBA-Associated Remodeling in Calcific Aortic Valve Disease. Arteriosclerosis, thrombosis, and vascular biology 0 42059080
2026 Correction: Spatial transcriptomics reveals Inhba/Smad2/E2f4 axis in Lrp2high thecal cell proliferation in androgen-induced PCOS mice. Frontiers in cell and developmental biology 0 42111260
2026 A multi-omics dissection of INHBA+ CAF-mediated epithelial-mesenchymal transition and immune suppression in colorectal cancer. Journal of translational medicine 0 42143353
2026 G-CSF enhances neutrophil function with potential involvement of INHBA during Aspergillus fumigatus infection. International journal of medical microbiology : IJMM 0 42173078
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
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

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