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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2019
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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. |
format | Online Article Text |
id | pubmed-6557201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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