Mobile website
Archive > Volume 29 Issue 12 > 2022,29(12):1076-1086. DOI:10.3872/j.issn.1007-385X.2022.12.003 Prev Next
Basic Research
Methyltransferase-like 3 affects glycolysis and proliferation of esophageal squamous cell carcinoma cells by regulating the GLUT4-mTORC1 axis
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective: To investigate the expression of methyltransferase-like 3 (METTL3) in esophageal squamous cell carcinoma (ESCC) tissue and cells and its effect on the glycolysis proliferation of ESCC cells as well as the potential molecular mechanisms. Methods: Based on the TCGA database, the expression of METTL3 and its possible enrichment pathway in ESCC were elucidated. Thirty-four ESCC tissues and corresponding paracancerous tissues were collected from surgical resections at the Affiliated Hospital of Beichuan Medical College between January 2021 and June 2021, the expression of METTL3 in ESCC tissues was verified by immunohistochemistry. The CCK-8 and colony formation assay were used to evaluate the change in the proliferation ability of ESCC cells after METTL3 knockdown. The expression level of m6A in total RNA of ESCC cells after METTL3 knockdown was detected by colorimetric method. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was used to detect the effect of METTL3 on the m6A modification level of glucose transporter 4 (GLUT4) mRNA. The biological mechanisms of METTL3 in the glycolysis metabolism of ESCC were evaluated using WB and qPCR. Results: The expression level of METTL3 was significantly increased in ESCC tissues as well as cell lines (all P<0.001). After the knockdown of METTL3, the proliferation ability of ESCC cells was significantly reduced, and the m6A modification level of total RNA was significantly reduced (all P<0.001). In addition, knockdown of METTL3 significantly inhibited the m6A modification level of GLUT4 mRNA in KYSE150 and TE-1 cells (all P<0.01), inhibited glucose uptake and lactate release by down-regulating GLUT4 expression (all P<0.01), and finally down-regulated the activity of mTORC1 pathway and inhibited the proliferation of ESCC cells. Moreover, a synergetic effect was found in METTL3-depleted ESCC cells combined with mTORC1 pathway inhibitor. Conclusion: METTL3-mediated m6A modification promotes glycolysis and proliferation of ESCC cells by regulating the GLUT4-mTORC1 signaling axis.
Keywords:
Project Supported:
Clc Number:
