Affinage

MYEOV

Myeloma-overexpressed gene protein · UniProt Q96EZ4

Length
313 aa
Mass
33.6 kDa
Annotated
2026-06-10
24 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYEOV is a primate-specific 11q13 gene that functions as a context-dependent oncogenic regulator of transcription, acting both as a protein and as a non-coding RNA to drive cancer cell proliferation, invasion, and migration across multiple tumor types (PMID:32879444, PMID:34930894). It was first recovered as a candidate transforming gene in a t(11;14)(q13;q32) myeloma setting, where overexpression is driven by juxtaposition of IgH Eµ or Eα enhancers to the MYEOV locus (PMID:10753852); however, MYEOV cDNA alone does not transform NIH/3T3 cells, the original signal instead arising from co-transferred FGF4 located ~9 kb away (PMID:17390055). As a nuclear protein, MYEOV physically associates with transcription factors to amplify their output: it binds SOX9 and enhances its DNA-binding at the HES1 enhancer to increase HES1 transcription (PMID:32879444), and it associates with MYC to promote MYC enrichment at the miR-17-5p/miR-93-5p promoters, upregulating these miRNAs (PMID:34930894). Independent of protein-coding capacity, the MYEOV transcript acts as a competing endogenous RNA that sequesters miR-30c-2-3p, de-repressing TGFBR2 and USP15 to constitutively activate TGF-β signaling (PMID:30181549). MYEOV expression is itself heavily regulated: at the transcript level by DNA methylation (PMID:12202983), by NSUN2-mediated m5C stabilization and miR-490-5p targeting (PMID:40743298, PMID:31894478), and by super-enhancer elements (PMID:38490328); at the translational level, upstream ORFs in its long 5'-UTR repress translation of the downstream MYEOV ORF (PMID:16275643). Beyond cancer, MYEOV is a downstream effector of PAX6/KLF4 supporting proliferation of the corneal epithelial transient amplifying compartment (PMID:41186354), and its loss can trigger ferroptosis via SMPD1-mediated autophagic GPX4 degradation (PMID:38490328).

Mechanistic history

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

    Established MYEOV as a candidate oncogene activated by IgH enhancer juxtaposition in t(11;14) myeloma, framing it as a 11q13 deregulation target.

    Evidence NIH/3T3 tumorigenicity assay and DNA fiber FISH mapping of IgH Eµ/Eα enhancer juxtaposition in myeloma cell lines

    PMID:10753852

    Open questions at the time
    • The transformation readout did not isolate MYEOV from neighboring 11q13 loci
    • No protein-level mechanism defined
  2. 2002 Medium

    Showed MYEOV expression is controlled by DNA methylation even within amplified loci, explaining variable expression despite 11q13 gain.

    Evidence 5-aza-2'-deoxycytidine demethylation with expression rescue and copy-number analysis in esophageal squamous carcinoma lines

    PMID:12202983

    Open questions at the time
    • Did not map the specific methylated promoter region
    • No functional consequence of restored expression tested
  3. 2005 High

    Resolved how MYEOV protein output is set post-transcriptionally, showing uORFs in its long 5'-UTR repress translation and that prior IRES interpretation reflected cryptic promoter activity.

    Evidence In vitro transcription/translation, dicistronic and direct-RNA reporter constructs, uAUG mutagenesis

    PMID:16275643

    Open questions at the time
    • Conditions relieving uORF repression in tumors not identified
    • Endogenous protein levels not quantified across tissues
  4. 2006 Low

    Provided the first loss-of-function evidence that MYEOV supports cancer cell proliferation and invasion in gastric and colon cancer.

    Evidence siRNA knockdown with proliferation and invasion assays in gastric and colon cancer lines

    PMID:16552434 PMID:16678123

    Open questions at the time
    • Single siRNA approach without rescue
    • No molecular pathway placement
  5. 2007 Medium

    Corrected the original transformation claim by showing MYEOV cDNA alone is non-transforming, the prior signal arising from co-transferred FGF4.

    Evidence Sequencing, Southern and Northern analysis of tertiary NIH/3T3 transfectants

    PMID:17390055

    Open questions at the time
    • Does not exclude MYEOV oncogenic activity in other assay contexts
    • Negative result confined to NIH/3T3 system
  6. 2010 Low

    Linked MYEOV to migration and placed it downstream of PGE2 signaling in colorectal cancer.

    Evidence siRNA knockdown with scratch wound assay and PGE2-induction qPCR

    PMID:20569498

    Open questions at the time
    • Mechanism of PGE2-dependent MYEOV induction not defined
    • Single migration readout
  7. 2011 Low

    Extended MYEOV's proliferative role to neuroblastoma driven by 11q13 chromosomal gain.

    Evidence siRNA knockdown and proliferation assay in NB-19 cells

    PMID:21624008

    Open questions at the time
    • Single method without rescue
    • No downstream effectors identified
  8. 2018 Medium

    Defined a protein-independent function: the MYEOV transcript acts as a ceRNA sponging miR-30c-2-3p to activate TGF-β signaling, establishing it as a coding/non-coding bifunctional oncogene.

    Evidence miRNA luciferase reporters, ORF-mutant constructs, and TGFBR2/USP15 expression analysis in NSCLC

    PMID:30181549

    Open questions at the time
    • Relative contribution of ceRNA versus protein function in vivo unclear
    • Single cancer-type context
  9. 2020 Medium

    Identified the first direct protein partner, showing nuclear MYEOV binds SOX9 to enhance its DNA-binding and HES1 transcription in pancreatic cancer.

    Evidence Co-IP, nuclear fractionation, HES1-enhancer ChIP, and HES1 knockdown rescue in vitro and in vivo

    PMID:32879444

    Open questions at the time
    • Structural basis of the MYEOV–SOX9 interaction unknown
    • How MYEOV potentiates DNA binding biochemically not resolved
  10. 2020 Medium

    Placed MYEOV under direct miRNA control, with miR-490-5p targeting MYEOV mRNA to mediate tumor suppression in neuroblastoma.

    Evidence Luciferase reporter validation plus knockdown/overexpression rescue with proliferation, cycle, and apoptosis assays

    PMID:31894478

    Open questions at the time
    • Whether targeting affects protein or ceRNA function not distinguished
    • Single cell-line context
  11. 2021 Medium

    Identified a second nuclear partner, showing MYEOV associates with MYC to promote MYC occupancy at miR-17-5p/miR-93-5p promoters.

    Evidence Co-IP, ChIP at miRNA promoters, miRNA-seq and transcriptomics with knockdown/overexpression in vitro and in vivo

    PMID:34930894

    Open questions at the time
    • Direct versus indirect MYEOV–MYC binding not biochemically resolved
    • Mechanism of enhanced MYC recruitment unknown
  12. 2023 Low

    Connected MYEOV to folate metabolism, placing it upstream of MTHFD2 and the c-Myc/mTORC1 axis in pancreatic cancer.

    Evidence siRNA knockdown with transcriptome and promoter methylation analysis

    PMID:36698109

    Open questions at the time
    • Expression-based placement without direct interaction or reconstitution
    • Causal versus correlative effect on metabolism unclear
  13. 2024 Medium

    Revealed that MYEOV loss triggers ferroptosis via SMPD1-mediated autophagic GPX4 degradation and confirmed super-enhancer-driven transcription in LUAD.

    Evidence siRNA, CRISPRi, ChIP-PCR, dual-luciferase, H3K27ac ChIP-seq, Hi-C, ferroptosis marker quantification, and in vivo growth

    PMID:38490328

    Open questions at the time
    • How MYEOV restrains SMPD1/autophagy mechanistically not defined
    • Direct molecular target of MYEOV in this pathway unknown
  14. 2025 Low

    Added a TGF-β–H3K4me3–MMP9 epigenetic axis and m5C-based transcript stabilization, extending MYEOV's invasion-promoting role to bladder cancer.

    Evidence Knockdown/overexpression, MMP9 promoter and rescue assays, and NSUN2 m5C analysis

    PMID:40743298

    Open questions at the time
    • Mechanistic link inferred from markers without reconstitution
    • How MYEOV drives H3K4me3 deposition at MMP9 not shown
  15. 2025 Medium

    Established a non-malignant physiological role, placing MYEOV downstream of PAX6/KLF4 in maintaining the corneal epithelial transient amplifying compartment.

    Evidence siRNA knockdown of PAX6/KLF4/MYEOV with western blot, colony-forming, EdU, immunostaining, and scRNA-seq analysis

    PMID:41186354

    Open questions at the time
    • Molecular partners of MYEOV in corneal epithelium not identified
    • Whether the nuclear transcription-factor mechanism operates here untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MYEOV physically engages its transcription-factor partners and what its biochemical activity is at the molecular level remain undefined.
  • No structure or defined enzymatic/binding domain
  • No reciprocal or reconstituted validation of SOX9/MYC interactions
  • Relative weight of protein versus ceRNA function in vivo unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1643685 Disease 1 R-HSA-5357801 Programmed Cell Death 1
Partners
MYCSOX9

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 MYEOV was identified as a transforming gene by the NIH/3T3 tumorigenicity assay using DNA from a gastric carcinoma. In a subset of t(11;14)(q13;q32)-positive multiple myeloma cell lines, MYEOV overexpression was caused by juxtaposition of either the 5' Eμ enhancer or the 3' Eα enhancer of the IgH locus to the MYEOV gene, as mapped by DNA fiber FISH. NIH/3T3 tumorigenicity assay, Northern blot, DNA fiber FISH with IgH enhancer probes Blood Medium 10753852
2005 MYEOV protein synthesis is controlled by upstream open reading frames (uORFs) in its long 5'-UTR. Direct RNA transfection and mutagenesis of upstream AUG triplets demonstrated that these uAUGs abrogate translation of the downstream MYEOV ORF. The 5'-UTR also harbors cryptic promoter activity, which confounded initial IRES interpretations; in vitro transcription/translation and promoterless dicistronic constructs revealed this promoter activity rather than a true IRES. In vitro transcription/translation assay, Northern blot, monocistronic and dicistronic reporter constructs (transfection and direct RNA transfection), uAUG mutagenesis The Journal of Biological Chemistry High 16275643
2007 MYEOV cDNA alone failed to induce tumour formation in NIH/3T3 cells. The original tumorigenicity assay result was explained by co-transfer of the human oncogene HST/FGF4, located ~9 kb from MYEOV at 11q13, which underwent rearrangement and expression in the transfectants. Sequence analysis of tertiary transfectants, Southern blot, Northern blot Oncology reports Medium 17390055
2006 siRNA-mediated knockdown of MYEOV in gastric cancer cell lines resulted in decreased cell proliferation and invasion in vitro. siRNA knockdown, cell proliferation assay, invasion assay British journal of cancer Low 16552434
2006 siRNA-mediated knockdown of MYEOV in colon cancer cells resulted in a 48% decrease in cell proliferation and a 36% decrease in cell invasion in vitro. siRNA knockdown, cell proliferation assay, invasion assay Biochemical and biophysical research communications Low 16678123
2010 siRNA-mediated MYEOV knockdown significantly reduced colorectal cancer cell migration in a scratch wound healing assay. Additionally, treatment of CRC cells with PGE2 dose-dependently upregulated MYEOV expression, indicating that MYEOV expression is regulated by PGE2 signaling. siRNA knockdown, scratch wound healing assay, real-time PCR after PGE2 treatment Journal of experimental & clinical cancer research Low 20569498
2011 siRNA-mediated knockdown of MYEOV in NB-19 neuroblastoma cells (which overexpress MYEOV due to 11q13 chromosomal gain) resulted in a significant decrease in cell proliferation. siRNA knockdown, cell proliferation assay Cancer science Low 21624008
2002 MYEOV is epigenetically silenced by DNA methylation in a subset of esophageal squamous cell carcinoma cell lines that carry 11q13 amplification; treatment with the demethylating agent 5-aza-2'-deoxycytidine restored MYEOV expression in these lines. 5-aza-2'-deoxycytidine demethylation treatment, Northern blot/expression analysis, copy number analysis Journal of human genetics Medium 12202983
2018 The MYEOV transcript acts as a competing endogenous RNA (ceRNA) to sequester miR-30c-2-3p, thereby de-repressing TGFBR2 and USP15 mRNAs and constitutively activating TGF-β signaling in NSCLC cells. This pro-metastatic function was shown to be independent of MYEOV protein-coding capacity. miRNA luciferase reporter assay, rescue/overexpression experiments, MYEOV ORF-mutant constructs, miR-30c-2-3p manipulation, TGFBR2/USP15 expression analysis Oncogene Medium 30181549
2020 MYEOV physically interacts with the transcription factor SOX9 primarily in the nuclei of pancreatic ductal adenocarcinoma cells, enhancing SOX9 DNA-binding ability to the HES1 enhancer and increasing HES1 transcription, without altering SOX9 protein levels or subcellular localization. HES1 knockdown partially abrogated the oncogenic effect of MYEOV. Co-immunoprecipitation, nuclear fractionation/co-localization, ChIP assay on HES1 enhancer, HES1 knockdown rescue, overexpression/knockdown in vitro and in vivo Oncogene Medium 32879444
2020 miR-490-5p directly targets MYEOV mRNA as demonstrated by luciferase reporter assay. MYEOV knockdown mimicked the tumor-suppressive effects of miR-490-5p overexpression (reduced proliferation, migration, invasion, G0/G1 arrest, apoptosis), while MYEOV overexpression rescued these effects in neuroblastoma cells. Luciferase reporter assay, siRNA knockdown, overexpression rescue, CCK-8, flow cytometry, transwell assay Human cell Medium 31894478
2021 MYEOV associates with the transcription factor MYC in the nucleus of pancreatic cancer cells (identified by Co-IP), and this association promotes enrichment of MYC at the promoter regions of miR-17-5p and miR-93-5p, thereby upregulating their expression and driving cell proliferation, invasion, and migration. Co-immunoprecipitation, ChIP at miRNA promoters, miRNA-seq, transcriptome analysis, knockdown/overexpression experiments in vitro and in vivo Cell death & disease Medium 34930894
2023 MYEOV knockdown in pancreatic cancer cells suppressed expression of MTHFD2 and other folate metabolism-related enzyme genes, and restored expression of c-Myc and mTORC1 repressors, placing MYEOV upstream of the folate cycle/c-Myc/mTORC1 oncogenic pathway. siRNA knockdown, transcriptome/gene expression analysis, promoter methylation analysis BMC cancer Low 36698109
2024 MYEOV knockdown in lung adenocarcinoma cells induced ferroptosis, characterized by increased intracellular Fe2+, ROS, and lipid peroxidation, and altered marker proteins (SLC7A11, GPX4, FTH1, ACSL4). Mechanistically, SMPD1-induced autophagic degradation of GPX4 was identified as the critical process mediating ferroptosis upon MYEOV knockdown. Super-enhancer elements drive MYEOV transcriptional activation in LUAD as confirmed by CRISPRi, ChIP-PCR, and dual-luciferase reporter assays. siRNA knockdown, CRISPRi, ChIP-PCR, dual-luciferase reporter, H3K27ac ChIP-seq, Hi-C, ferroptosis marker quantification (Fe2+, ROS, lipid peroxidation), western blot, in vivo tumor growth Cancer letters Medium 38490328
2025 MYEOV activates the TGF-β–H3K4me3 signaling axis to directly enhance MMP9 promoter activity through epigenetic modification, thereby upregulating MMP9 expression and promoting bladder cancer cell proliferation and invasion. Restoration of MMP9 expression counteracted the effects of MYEOV knockdown. Additionally, NSUN2 stabilizes MYEOV mRNA via m5C methylation, increasing MYEOV expression in bladder cancer. Knockdown/overexpression, MMP9 promoter activity assay, MMP9 rescue experiment, m5C methylation analysis, in vitro proliferation and invasion assays Molecular carcinogenesis Low 40743298
2025 In the human cornea, MYEOV expression is regulated by the transcription factors PAX6 and KLF4 (knockdown of either reduced MYEOV and KRT12 protein levels). MYEOV knockdown decreased corneal epithelial cell proliferation, indicating a role in maintaining the transient amplifying cell compartment of the corneal epithelium. siRNA knockdown of PAX6, KLF4, and MYEOV; western blot; colony-forming assay; EdU proliferation assay; immunostaining; single-cell RNA-seq data analysis Investigative ophthalmology & visual science Medium 41186354

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32). Blood 102 10753852
2006 Net1 and Myeov: computationally identified mediators of gastric cancer. British journal of cancer 66 16552434
2006 ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion. Biochemical and biophysical research communications 48 16678123
2002 MYEOV: a candidate gene for DNA amplification events occurring centromeric to CCND1 in breast cancer. International journal of cancer 46 12448002
2018 MYEOV functions as an amplified competing endogenous RNA in promoting metastasis by activating TGF-β pathway in NSCLC. Oncogene 45 30181549
2002 MYEOV, a gene at 11q13, is coamplified with CCND1, but epigenetically inactivated in a subset of esophageal squamous cell carcinomas. Journal of human genetics 40 12202983
2011 Aberrations of NEGR1 on 1p31 and MYEOV on 11q13 in neuroblastoma. Cancer science 34 21624008
2020 MYEOV increases HES1 expression and promotes pancreatic cancer progression by enhancing SOX9 transactivity. Oncogene 32 32879444
2010 MYEOV (myeloma overexpressed gene) drives colon cancer cell migration and is regulated by PGE2. Journal of experimental & clinical cancer research : CR 26 20569498
2005 Control of MYEOV protein synthesis by upstream open reading frames. The Journal of biological chemistry 18 16275643
2024 Super-enhancer mediated upregulation of MYEOV suppresses ferroptosis in lung adenocarcinoma. Cancer letters 15 38490328
2020 MiR-490-5p functions as tumor suppressor in childhood neuroblastoma by targeting MYEOV. Human cell 14 31894478
2015 Adaptive Evolution Coupled with Retrotransposon Exaptation Allowed for the Generation of a Human-Protein-Specific Coding Gene That Promotes Cancer Cell Proliferation and Metastasis in Both Haematological Malignancies and Solid Tumours: The Extraordinary Case of MYEOV Gene. Scientifica 13 26568894
2021 The MYEOV-MYC association promotes oncogenic miR-17/93-5p expression in pancreatic ductal adenocarcinoma. Cell death & disease 12 34930894
2023 MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway. BMC cancer 9 36698109
2016 MYEOV gene overexpression in primary plasma cell leukemia with t(11;14)(q13;q32). Oncology letters 8 27446453
2007 Rearrangement and expression of myeov and hst in NIH/3T3 transfectants: a caveat for the interpretation of DNA transfection analyses. Oncology reports 7 17390055
2022 Identification of MYEOV-Associated Gene Network as a Potential Therapeutic Target in Pancreatic Cancer. Cancers 6 36358856
2023 MYEOV with High Frequencies of Mutations in Head and Neck Cancers Facilitates Cancer Cell Malignant Behaviors. Biochemical genetics 3 37667096
2024 Evolutionarily conserved enhancer-associated features within the MYEOV locus suggest a regulatory role for this non-coding DNA region in cancer. Frontiers in cell and developmental biology 2 39139450
2025 HHLA3 Silencing Suppresses KRAS-Mutant Non-Small-Cell Lung Cancer Cell Progression Through Triggering MYEOV-Mediated Ferroptosis. Journal of biochemical and molecular toxicology 1 40262052
2025 The role of MYEOV gene: a review and future directions. Frontiers in oncology 1 40535130
2025 MYEOV Facilitates the Progression of Bladder Cancer by Upregulating MMP9 Via the TGF-β-H3K4me3 Epigenetic Axis. Molecular carcinogenesis 1 40743298
2025 MYEOV Is a Novel Marker of Differentiated Corneal Epithelium. Investigative ophthalmology & visual science 1 41186354

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