Modomics - A Database of RNA Modifications

Published on Aug. 1, 2019 in Melanoma Res volume 29(4).

PubMed ID: 30762711

DOI: 10.1097/CMR.0000000000000580


The development of immunotherapy has improved the treatment of melanoma; however,resistance and frequent recurrence persist and remain a major problem.N-methyladenosine (mA) is the most abundant epitranscriptomic mark on mRNA and isessential for various physiological processes; however, its role in melanoma isunknown. Utilizing human normal melanocyte and melanoma cell lines, we analyzed theexpression of METTL3 by quantitative RT-PCR. We inhibited the METTL3 expression byshRNA and analyzed the effects on melanoma cell proliferation, colony formationability, and invasion. Finally, we assessed the role of METTL3 by using wild-typeand mA catalytic site mutant METTL3. Melanoma cell lines express higher levels ofMETTL3, as compared with normal melanocytes. Interestingly, silencing of METTL3 geneexpression in melanoma cells resulted in decreased mA activity, colony formation andinvasiveness, while its overexpression led to increased mA activity, colonyformation and invasion. METTL3 overexpression promotes accumulation of MMP2 andN-cadherin in melanoma cells. Strikingly, the overexpression of mA catalytic sitemutant METTL3 was unable to produce a similar increase in MMP2 expression,suggesting that mA activity of METTL3 is important for melanoma cell invasiveness.Our results for the first time uncover the role of mA modification in melanoma cellbiology. We show that METTL3 is upregulated in human melanoma and plays a role ininvasion/migration through MMP2. These findings provide the framework for thedevelopment and use of METTL3 inhibitors in melanoma treatment.