Transcriptomic studies provide insights into the tumor suppressive role of miR-146a-5p in non-small cell lung cancer (NSCLC) cells

Abstract

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-κB 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-β, HIF-1α, and various cyclins. miR-146a-5p transfection also reduced expression and cellular release of the chemokine CCL2, and this effect was mediated through the 3ʹ 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.

TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2

“…MicroRNAs (miRNAs or miRs) are a category of small non-coding RNAs approximately 20 nucleotides in length ( 15 ). Previous studies have indicated that miRNAs, such as miR-214, miR-153 and miR-146a-5p, play important roles during the progression of various types of cancer ( 16 - 18 ). As a type of miRNA, miR-197-3p has been reported to facilitate the proliferation of breast cancer cells ( 19 ).…”

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

“…MiR‐146a‐5p is another onco‐suppressor miR that is affected by CT in NSCLC cells. MiR‐146a‐5p interferes with metabolism of cancer cells and also, impairs their proliferation via targeting NF‐κB and EGFR signaling pathways (Iacona, Monteleone, Lemenze, Cornett, & Lutz, 2019). In breast cancer cells, the expression of interleukin‐1 receptor‐associated kinase 1 (IRAK1) undergoes upregulation.…”

Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 infections to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease patients

“…The identified TFs, such as FOSL1, DAXX, HSPB6, CFB, FLNC, VARS2, TMEM238, PSMB8, EPN3, and DNAAF1, are associated with diffident types of respiratory diseases. Further, some miRNAs involve in lung cancer (e.g., miR-146a-5p, hsa-mir-34a-5p, hsa-mir-873-5p, hsa-miR-195-5p, hsa-mir-335-5p) [ 71–75 ], immunity disorder (e.g., hsa-mir-124-3p, hsa-miR-155-5p) [ 76 , 77 ], and different chronic cancer (e.g., hsa-mir-1-3p, hsa-mir-765, hsa-mir-29a-5p, hsa-mir-142-3p) [ 78–81 ]. Gene-TFs and gene-miRNAs basically target main proteins to change the appearance in the progress of particular diseases.…”

“…Furthermore, hsa-mir-941, hsa-mir-374a-5p, hsa-mir-17-3p, and hsa-mir-129-2-3p are targeted by the FLNC [ 82 , 83 ]. Remarkably, we also predicted four miRNAs (hsa-mir-16-5p, hsa-let-7e-5p, hsa-mir-26a-5p, and hsa-mir-146a-5p) that are associated with different genes of IPF and COPD [ 71 ]. Most of the miRNAs are related to cancer tissue and lead to the different types of cancer in the human body, especially lung cancer.…”