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Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53

Mutations in the TP53 gene are one of the most frequent events in cancers. Certain missense mutant p53 proteins gain oncogenic functions (gain-of-functions) and drive tumorigenesis. Apart from the coding genes, a few non-coding microRNAs (miRNAs) are implicated in mediating mutant p53-driven cancer...

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Autores principales: Datta, Arindam, Das, Pijush, Dey, Sanjib, Ghuwalewala, Sangeeta, Ghatak, Dishari, Alam, Sk. Kayum, Chatterjee, Raghunath, Roychoudhury, Susanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895929/
https://www.ncbi.nlm.nih.gov/pubmed/31661871
http://dx.doi.org/10.3390/genes10110852
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author Datta, Arindam
Das, Pijush
Dey, Sanjib
Ghuwalewala, Sangeeta
Ghatak, Dishari
Alam, Sk. Kayum
Chatterjee, Raghunath
Roychoudhury, Susanta
author_facet Datta, Arindam
Das, Pijush
Dey, Sanjib
Ghuwalewala, Sangeeta
Ghatak, Dishari
Alam, Sk. Kayum
Chatterjee, Raghunath
Roychoudhury, Susanta
author_sort Datta, Arindam
collection PubMed
description Mutations in the TP53 gene are one of the most frequent events in cancers. Certain missense mutant p53 proteins gain oncogenic functions (gain-of-functions) and drive tumorigenesis. Apart from the coding genes, a few non-coding microRNAs (miRNAs) are implicated in mediating mutant p53-driven cancer phenotypes. Here, we identified miRNAs in mutant p53(R273H) bearing non-small cell lung carcinoma (NSCLC) cells while using small RNA deep sequencing. Differentially regulated miRNAs were validated in the TCGA lung adenocarcinoma patients with p53 mutations and, subsequently, we identified specific miRNA signatures that are associated with lymph node metastasis and poor survival of the patients. Pathway analyses with integrated miRNA-mRNA expressions further revealed potential regulatory molecular networks in mutant p53 cancer cells. A possible contribution of putative mutant p53-regulated miRNAs in epithelial-to-mesenchymal transition (EMT) is also predicted. Most importantly, we identified a novel miRNA from the unmapped sequencing reads through a systematic computational approach. The newly identified miRNA promotes proliferation, colony-forming ability, and migration of NSCLC cells. Overall, the present study provides an altered miRNA expression profile that might be useful in biomarker discovery for non-small cell lung cancers with TP53 mutations and discovers a hitherto unknown miRNA with oncogenic potential.
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spelling pubmed-68959292019-12-24 Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53 Datta, Arindam Das, Pijush Dey, Sanjib Ghuwalewala, Sangeeta Ghatak, Dishari Alam, Sk. Kayum Chatterjee, Raghunath Roychoudhury, Susanta Genes (Basel) Article Mutations in the TP53 gene are one of the most frequent events in cancers. Certain missense mutant p53 proteins gain oncogenic functions (gain-of-functions) and drive tumorigenesis. Apart from the coding genes, a few non-coding microRNAs (miRNAs) are implicated in mediating mutant p53-driven cancer phenotypes. Here, we identified miRNAs in mutant p53(R273H) bearing non-small cell lung carcinoma (NSCLC) cells while using small RNA deep sequencing. Differentially regulated miRNAs were validated in the TCGA lung adenocarcinoma patients with p53 mutations and, subsequently, we identified specific miRNA signatures that are associated with lymph node metastasis and poor survival of the patients. Pathway analyses with integrated miRNA-mRNA expressions further revealed potential regulatory molecular networks in mutant p53 cancer cells. A possible contribution of putative mutant p53-regulated miRNAs in epithelial-to-mesenchymal transition (EMT) is also predicted. Most importantly, we identified a novel miRNA from the unmapped sequencing reads through a systematic computational approach. The newly identified miRNA promotes proliferation, colony-forming ability, and migration of NSCLC cells. Overall, the present study provides an altered miRNA expression profile that might be useful in biomarker discovery for non-small cell lung cancers with TP53 mutations and discovers a hitherto unknown miRNA with oncogenic potential. MDPI 2019-10-28 /pmc/articles/PMC6895929/ /pubmed/31661871 http://dx.doi.org/10.3390/genes10110852 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Datta, Arindam
Das, Pijush
Dey, Sanjib
Ghuwalewala, Sangeeta
Ghatak, Dishari
Alam, Sk. Kayum
Chatterjee, Raghunath
Roychoudhury, Susanta
Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53
title Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53
title_full Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53
title_fullStr Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53
title_full_unstemmed Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53
title_short Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53
title_sort genome-wide small rna sequencing identifies micrornas deregulated in non-small cell lung carcinoma harboring gain-of-function mutant p53
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895929/
https://www.ncbi.nlm.nih.gov/pubmed/31661871
http://dx.doi.org/10.3390/genes10110852
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