ArticleGenes & genomics2022
METTL3 m6A-dependently promotes miR-21-5p maturation to accelerate choriocarcinoma progression via the HIF1AN-induced inactivation of the HIF1A/VEGF pathway.
Article in Genes & genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Emerging roles of mJournal of assisted reproduction and genetics · 2026Review
- Unravelling Multilayered RNA Modification Networks in Female Reproduction and Obstetric/Gynaecologic Disorders.Biomolecules · 2026Review
- Phospholipase Cε1 activates Rap1 signaling pathway to promote proliferation, EMT and angiogenesis of choriocarcinoma cells.Molecular biology reports · 2025Article
- METTL3: a multifunctional regulator in diseases.Molecular and cellular biochemistry · 2025Review
- Hsa-miR-21-5p and Hsa-miR-145-5p Expression: From Normal Tissue to Malignant Changes-Context-Dependent Correlation with Estrogen- and Hypoxia-Vascularization-Related Pathways Genes: A Pilot Study.International journal of molecular sciences · 2025Article
- Epitranscriptomic regulation of HIF-1: bidirectional regulatory pathways.Molecular medicine (Cambridge, Mass.) · 2025Review
- Epigenetic regulation in female reproduction: the impact of m6A on maternal-fetal health.Cell death discovery · 2025Review
- The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy.Frontiers in cell and developmental biology · 2025Review
- METTL3 accelerates staphylococcal protein A (SpA)-induced osteomyelitis progression by regulating m6A methylation-modified miR-320a.Journal of orthopaedic surgery and research · 2024Article
- Molecular characterization and function of hif1a and fih1 in response to acute thermal stress in American shad (Alosa sapidissima).Fish physiology and biochemistry · 2024Article
- Tumor-associated macrophage-derived exosomal miR21-5p promotes tumor angiogenesis by regulating YAP1/HIF-1α axis in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Coilin mediates m6A RNA methylation through phosphorylation of METTL3.Biology open · 2023Article
- Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway.Open medicine (Warsaw, Poland) · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGestational choriocarcinoma is a highly malignant neoplastic disease derived from pathological changes in trophoblastic cells. Recent evidences have shown that N6-methyladenosine (m6A) modifications play important role in modulating the development of multiple cancers, but the detailed mechanisms by which m6A-mediated choriocarcinoma progression have not been fully delineated.
objectivesThis study aimed to investigate the role of m6A in choriocarcinoma and reveal its underlying molecular mechanisms.
methodsThe expression of METTL3, miR-21-5p and HIF1AN was detected using RT-qPCR in tissues and cells. The protein expression of METTL3, HIF1AN, HIF1A and VEGF were measured by western blot. The luciferase reporter assays and RNA immunoprecipitation (RIP) were used to verify the relationship between miR-21-5p and HIF1AN. The CCK-8, colony formation and transwell assays were used to detected cell proliferation and cell migration, respectively.
resultsHere, we demonstrated that the m6A methyltransferase-like 3 (METTL3) was aberrantly high-expressed in the clinical choriocarcinoma tissues and choriocarcinoma cell lines compared to the corresponding normal counterparts. The following functional experiments verified that silencing of METTL3 suppressed cell proliferation, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis in vitro and in vivo to hamper the aggressiveness of choriocarcinoma. Next, the mechanical experiments confirmed that METTL3 promoted the maturation of miR-21-5p in an m6A-dependent manner, and elevated miR-21-5p subsequently degraded its downstream hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by targeting its 3' untranslated regions (3'-UTR), resulting in the activation of the tumor-promoting HIF1A/VEGF pathway. Finally, the rescuing experiments verified that METTL3 ablation-induced inhibitory effects on the malignant phenotypes in choriocarcinoma were all abrogated by both miR-21-5p overexpression and HIF1AN downregulation.
conclusionsCollectively, this study firstly reported the involvement of the METTL3/m6A/miR-21-5p/HIF1AN signaling cascade in regulating the progression of choriocarcinoma, which provided novel biomarkers for the diagnosis and treatment of this disease.
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