Dissecting the role of RNA modification regulatory proteins in melanoma
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Parmanand Malvi1, Biao Wang1, Shreni Shah1 and Romi Gupta1,2
1 Department of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA
2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA
Keywords: RNA modifications; epitranscriptome; melanoma; MAPK; BRAF mutant melanoma
Received: November 08, 2018 Accepted: April 29, 2019 Published: June 04, 2019
Melanoma is the deadliest form of skin cancer. Despite recent advances in medicine and the development of new treatments for melanoma, cures remain elusive as acquired resistance to both targeted and immunotherapies are becoming common. Therefore, more studies are conducted to dissect underlying molecular mechanisms that drive melanoma growth in order to provide better therapeutic option. Here, employing a comprehensive and unbiased analysis of different RNA modification regulatory proteins using various publicly available databases we identify the most relevant RNA modifying proteins that plays crucial role in melanoma development. Our study started with the analysis of various genetic alterations (amplifications, mutations/deletion) as well as RNA overexpression of these RNA modification regulatory proteins in The Cancer Genome Atlas melanoma database. We then analyzed their expression in The Human Protein Atlas data. The result of analysis revealed that only a subset of RNA modification regulatory proteins are overexpressed in >75% of melanoma patient cases as compared to normal skin. However, when examined in Oncomine dataset we found only two genes (METTL4 and DNMT3A) were significantly overexpressed in melanoma samples versus normal skin samples and matched with the results of The Human Protein Atlas data. Therefore, we functionally validated METTL4 and DNMT3A using shRNA-mediated knockdown and found that their knockdown in melanoma cells led to melanoma cells growth inhibition. Collectively, in this study, we investigated the epitranscriptomic landscape of melanoma using various publicly available database and identified DNMT3A and METTL4 as the most relevant potential regulators of melanoma growth.
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