Abstract
Objectives: Methyltransferase-like 14 (METTL14) plays an epigenetic role in various cancer through N6-methyladenosine (m6A) modification. This study sought to analyze the mechanism of METTL14 in oral squamous cell carcinoma (OSCC) cell proliferation. Methods: Expression levels of METTL14, lncRNA metastasis associated with lung adenocarcinoma transcript 1 (lncRNA MALAT1), microRNA (miR)-224-5p, and histone lysine demethylase 2A (KDM2A) in OSCC tissues (N = 40), and cell lines (FaDu, SCC-25, CAL-27, and SCC-15) were detected. Cell viability and colony formation capacity were assessed. m6A level, stability, and subcellular localization of lncRNA MALAT1 were determined. Nude mouse xenograft tumor assay was performed to confirm the role of METTL14 in vivo. Results: METTL14 and lncRNA MALAT1 were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. Silencing METTL14 repressed OSCC cell viability and colony formation. Overexpression of MALAT1 and KDM2A or miR-224-5p downregulation reversed the inhibition of silencing METTL14 on OSCC cell proliferation. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1. MALAT1 is comparatively bound to miR-224-5p to promote KDM2A transcription. In vivo, METTL14 promoted tumor growth via regulating MALAT1/miR-224-5p/ KDM2A. Conclusions: Overall, our findings verified the therapeutic role of silencing METTL14 in OSCC treatment through the MALAT1/miR-224-5p/KDM2A axis.
| Original language | English |
|---|---|
| Pages (from-to) | 2012-2026 |
| Number of pages | 15 |
| Journal | Oral Diseases |
| Volume | 29 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jul 2023 |
Bibliographical note
Publisher Copyright:© 2022 Wiley Periodicals LLC.
Funding
Grants from the Southern Medical University Shenzhen Stomatology Hospital (Pingshan) ‐the dean’s scientific research fund project for Wu Xun. Grants from the Columbia University Irving Medical Center, the Columbia University College of Dental Medicine, and the Irving Institute for Clinical and Translational Research (UL1 TR001873), NIH/NIDCR (DE029546‐01), and the American Association of Cancer Research and The Mark Foundation for Cancer Research (20–60‐51‐MOME) to F.M‐H.
| Funders | Funder number |
|---|---|
| Southern Medical University Shenzhen Stomatology Hospital | |
| National Institutes of Health | |
| American Association for Cancer Research | |
| National Institute of Dental and Craniofacial Research | DE029546‐01 |
| College of Dental Medicine, Columbia University | |
| Irving Medical Center, Columbia University | |
| Mark Foundation For Cancer Research | 20–60‐51‐MOME |
| Institute for Clinical and Translational Research, University of Maryland, Baltimore | UL1 TR001873 |
ASJC Scopus Subject Areas
- General Dentistry
- Otorhinolaryngology
