The m6A Methyltransferase METTL3 Promotes Cisplatin Resistance and Invasion in Testicular Seminoma via BCL2

Abstract Background: Methyltransferase-like 3 (METTL3) involves in promoting tumor progression through tumor-related genes N6-methyladenosine (m6A) modification. Our previous study found that METTL3 plays an important role in seminoma chemosensitivity. BCL-2 is a key cause of cisplatin resistance in many tumors. Therefore, we want to explore whether METTL3 affects cisplatin resistance of seminoma by regulating BCL-2.Methods: In this study, we downregulated and overexpressed METTL3 in TCam-2 cisplatin resistant cells (TCam-2/CDDP). Then, m6A RNA methylation quantification of BCL-2 and cell viability assay, cell apoptosis analysis and cell invasion assay were investigated under the condition of with or without cis‐dichlorodiammine platinum (CDDP) treatment. Results: Consistent with our previous results, METTL3 significantly affects the chemosensitivity of TCam-2/CDDP. After METTL3 downregulated, the proliferation and anti-apoptosis ability of TCam-2/CDDP cells significantly weakened. Correspondingly, overexpression of METTL3 could promote the chemoresistance. However, the phenotype could be partly reversed by decreasing the expression of BCL-2. Moreover, we found that the m6A modification of BCL-2 is more abundant in cisplatin-resistant strains. Knockdown and overexpression of METTL3 significantly affected the m6A modification and the protein level of BCL-2 in TCam-2/CDDP. Finally, we found that METTL3 also promoted the invasion ability of TCam-2/CDDP cells via BCL2.Conclusion: This study revealed that METTL3 promotes anti-apoptosis and invasion of TCam-2/CDDP through BCL-2. And it indicated that METTL3 and BCL-2 may be an effective treatment target for CDDP-resistance seminoma.