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

AI Article Synopsis

  • Mutations in the p53 gene are common in cancers, leading to abnormal protein functions that promote tumor growth, particularly in non-small cell lung carcinoma (NSCLC).
  • The study identified specific microRNAs (miRNAs) linked to mutated p53 that are associated with lymph node metastasis and poor patient survival and validated these findings using patient data.
  • A new miRNA was discovered through a detailed computational analysis, which was found to enhance tumor cell proliferation, colony formation, and migration, suggesting its potential as a biomarker for NSCLC.

Article Abstract

Mutations in the 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 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 mutations and discovers a hitherto unknown miRNA with oncogenic potential.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895929PMC
http://dx.doi.org/10.3390/genes10110852DOI Listing

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