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Dissecting the role of RNA modification regulatory proteins in melanoma

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 mol...

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Autores principales: Malvi, Parmanand, Wang, Biao, Shah, Shreni, Gupta, Romi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557201/
https://www.ncbi.nlm.nih.gov/pubmed/31217906
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author Malvi, Parmanand
Wang, Biao
Shah, Shreni
Gupta, Romi
author_facet Malvi, Parmanand
Wang, Biao
Shah, Shreni
Gupta, Romi
author_sort Malvi, Parmanand
collection PubMed
description 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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spelling pubmed-65572012019-06-19 Dissecting the role of RNA modification regulatory proteins in melanoma Malvi, Parmanand Wang, Biao Shah, Shreni Gupta, Romi Oncotarget Research Paper 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. Impact Journals LLC 2019-06-04 /pmc/articles/PMC6557201/ /pubmed/31217906 Text en Copyright: © 2019 Malvi et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Malvi, Parmanand
Wang, Biao
Shah, Shreni
Gupta, Romi
Dissecting the role of RNA modification regulatory proteins in melanoma
title Dissecting the role of RNA modification regulatory proteins in melanoma
title_full Dissecting the role of RNA modification regulatory proteins in melanoma
title_fullStr Dissecting the role of RNA modification regulatory proteins in melanoma
title_full_unstemmed Dissecting the role of RNA modification regulatory proteins in melanoma
title_short Dissecting the role of RNA modification regulatory proteins in melanoma
title_sort dissecting the role of rna modification regulatory proteins in melanoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557201/
https://www.ncbi.nlm.nih.gov/pubmed/31217906
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