METTL14-Mediate the Biological Effects of EMT in Bladder Cancer Cells by Methylating SOX4 mRNA with m6A

Abstract

Objectives: Bladder Cancer (BC) is one of the most common malignant tumours of urinary system, with high rates of metastasis and mortality. Methyltransferase-like 14 (METTL14) is an RNA N6-adenosine methyltransferase that can affect the development of tumours by modifying RNA expression. The study aims to uncover the molecular mechanism and biological function of METTL14 in BC.Materials and Methods: qRT-PCR assays were employed METTL14 in BC cell lines. MeRIP-qPCR and RIP were used to verify that SRY-related high-mobility-group box 4 (SOX4) modification by m6A is a downstream target of METTL14.Results: Biological experiments in vitro have demonstrated the biological function of METTL14 on BC cells. In the MGH-U3 cell lines, the expression of METTL14 was significantly down-regulated (p < 0.001), while the expression of SOX4 was significantly up-regulated (p < 0.01). Intervention of METTL14 expression can affect cell proliferation, migration, invasion, apoptosis, as well as the expression of EMT proteins in BC cell lines (p < 0.05). In addition, METTL14 can affect the biological functions of MGH-U3 cells and the expression of EMT proteins through the m6A modification of SOX4.Conclusion: METTL14 overexpression inhibited the proliferation, migration, invasion, and promoted apoptosis in BC cells, and also downregulated the expression of EMT-related proteins, while these effects were abolished by silencing SOX2. This suggests that METTL14, through its influence on SOX4 m6A modification, plays a crucial role in regulating the biological functions of bladder cancer cells, indicating its potential as a therapeutic target for BC.

Keywords: METTL14; EMT; Bladder cancer; SOX4 mRNA; m6A