Journal
RNA BIOLOGY
Volume 16, Issue 12, Pages 1721-1732Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2019.1657351
Keywords
Inflammation; lung adenocarcinoma; microRNA; gene expression; RNA-Seq; post-transcriptional regulation; HuR; CCL2
Categories
Funding
- New Jersey Commission on Cancer Research
- American Heart Association [15GRNT23240019]
- National Institute Of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health [R01AR069044]
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Non-small cell lung cancer (NSCLC) is a complex disease in need of new methods of therapeutic intervention. Recent interest has focused on using microRNAs (miRNAs) as a novel treatment method for various cancers. miRNAs negatively regulate gene expression post-transcriptionally, and have become attractive candidates for cancer treatment because they often simultaneously target multiple genes of similar biological function. One such miRNA is miR-146a-5p, which has been described as a tumor suppressive miRNA in NSCLC cell lines and tissues. In this study, we performed RNA-Sequencing (RNA-Seq) analysis following transfection of synthetic miR-146a-5p in an NSCLC cell line, A549, and validated our data with Gene Ontology and qRT-PCR analysis of known miR-146a-5p target genes. Our transcriptomic data revealed that miR-146a-5p exerts its tumor suppressive function beyond previously reported targeting of EGFR and NF-kappa B signaling. miR-146a-5p mimic transfection downregulated arachidonic acid metabolism genes, the RNA-binding protein HuR, and many HuR-stabilized pro-cancer mRNAs, including TGF-beta, HIF-1 alpha, and various cyclins. miR-146a-5p transfection also reduced expression and cellular release of the chemokine CCL2, and this effect was mediated through the 3MODIFIER LETTER PRIME untranslated region of its mRNA. Taken together, our work reveals that miR-146a-5p functions as a tumor suppressor in NSCLC by controlling various metabolic and signaling pathways through direct and indirect mechanisms.
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