RNA m6A methyltransferase METTL3 regulates invasiveness of melanoma cells by matrix metallopeptidase 2

The development of immunotherapy has improved the treatment of melanoma; however, resistance and frequent recurrence persist and remain a major problem. N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark on mRNA and is essential for various physiological processes; however, its role in melanoma is unknown. Utilizing human normal melanocyte and melanoma cell lines, we analyzed the expression of METTL3 by quantitative RT-PCR. We inhibited the METTL3 expression by shRNA and analyzed the effects on melanoma cell proliferation, colony formation ability, and invasion. Finally, we assessed the role of METTL3 by using wild-type and m6A catalytic site mutant METTL3. Melanoma cell lines express higher levels of METTL3, as compared with normal melanocytes. Interestingly, silencing of METTL3 gene expression in melanoma cells resulted in decreased m6A activity, colony formation and invasiveness, while its overexpression led to increased m6A activity, colony formation and invasion. METTL3 overexpression promotes accumulation of MMP2 and N-cadherin in melanoma cells. Strikingly, the overexpression of m6A catalytic site mutant METTL3 was unable to produce a similar increase in MMP2 expression, suggesting that m6A activity of METTL3 is important for melanoma cell invasiveness. Our results for the first time uncover the role of m6A modification in melanoma cell biology. We show that METTL3 is upregulated in human melanoma and plays a role in invasion/migration through MMP2. T...
Source: Melanoma Research - Category: Cancer & Oncology Tags: Original Articles Source Type: research