ArticleMolecular cancer2020
METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer.
Article in Molecular cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 258 papers, 2 of them syntheses that pooled it.
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Who cites it
258 citing papers in PubMed, 2 syntheses or guidelines pooled it, 443 citations in OpenAlex.
- The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.Cell death & disease · 2024Pooled it
- Prognostic and clinicopathological value of m6A regulators in human cancers: a meta-analysis.Aging · 2022Pooled it
- Effects of Isorhapontigenin on Cell Viability, Colony-Forming Efficiency, and Ferroptosis via Methyltransferase-Like 14-Mediated mMolecular carcinogenesis · 2026Article
- Potential Role of METTL14 in Modulating Prostate Cancer Proliferation and Glycolysis Through m6A Modification of LINC01138.Applied biochemistry and biotechnology · 2026Article
- Ubiquitination and NOncology letters · 2026Review
- piR-26681 suppresses ovarian cancer progression by enhancing METTL3/METTL14-mediated mCellular & molecular biology letters · 2026Article
- Nanoparticle-based strategies targeting disulfidptosis, anoikis, and PANoptosis for enhanced cancer therapy.Journal of nanobiotechnology · 2026Review
- An m6A-programmed cell death signature predicts prognosis and identifies STK25 as a therapeutic target in colon adenocarcinoma.Oncology letters · 2026Article
- mCellular & molecular biology letters · 2026Article
- RNA modifications in cancer and their detection: a review.Japanese journal of clinical oncology · 2026Review
- MOncogene · 2026Article
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- Epigenetic regulation in cancer metastasis.Discover oncology · 2026Review
- Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK‒Nrf2 axis in multiple myeloma.Cell death & disease · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- m⁶A-Modified hsa_circ_0002694 facilitates OSCC progression via the METTL14/YTHDC1/miR-616-3p/c-Myc axis.Head & face medicine · 2026Article
- Matrine functions as a tumor inhibitor to influence proliferation, metastasis and glycolysis in colorectal cancer via depending on METTL14-mediated m6A methylation of MEX3A.Molecular and cellular biochemistry · 2026Article
- A bibliometric analysis of advances in N6‑methyladenosine research in colorectal cancer.Discover oncology · 2026Article
- m6A RNA modification and its emerging roles in diseases: recent advances and therapeutic implications.Journal of translational medicine · 2026Review
- Association of METTL14 expression with prognosis and immunotherapy in breast cancer.Translational cancer research · 2026Article
198 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide, and its main cause of death is distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, is involved in tumor progression via regulating RNA function. The goal of the study is to uncover the biological function and molecular mechanism of METTL14 in CRC.
methodsQuantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were employed to detect METTL14 and SOX4 in CRC cell lines and tissues. The biological functions of METTL14 were demonstrated using in vitro and in vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic RNA sequencing (RNA-Seq), m6A-RNA immunoprecipitation sequencing (MeRIP-Seq), RNA immunoprecipitation and luciferase reporter assays were used to explore the mechanism of METTL14 action.
resultsMETTL14 expression was significantly downregulated in CRC and decreased METTL14 was associated with poor overall survival (OS). Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation of histone H3 lysine 4 tri-methylation(H3K4me3) in the promoter of METTL14 inhibited METTL14 transcription. Functionally, we verified that METTL14 inhibited CRC cells migration, invasion and metastasis through in vitro and in vivo assays, respectively. Furthermore, we identified SRY-related high-mobility-group box 4(SOX4) as a target of METTL14-mediated m6A modification. Knockdown of METTL14 markedly abolished SOX4 mRNA m6A modification and elevated SOX4 mRNA expression. We also revealed that METTL14-mediated SOX4 mRNA degradation relied on the YTHDF2-dependent pathway. Lastly, we demonstrated that METTL14 might inhibit CRC malignant process partly through SOX4-mediated EMT process and PI3K/Akt signals.
conclusionsDecreased METTL14 facilitates tumor metastasis in CRC, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for CRC.
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