AUTHOR=Liu Xiangdong , Liu Bo , Li Ruihua , Wang Fei , Wang Ning , Zhang Maihe , Bai Yang , Wu Jin , Liu Liping , Han Dongyu , Li Zhiguang , Feng Bin , Zhou Guangbiao , Wang Shujing , Zeng Li , Miao Jian , Yao Yiqun , Liang Bin , Huang Lin , Wang Qi , Wu Yingjie TITLE=miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6 JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=8 YEAR=2020 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00847 DOI=10.3389/fcell.2020.00847 ISSN=2296-634X ABSTRACT=

Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world due to its often delayed diagnosis. Identification of biomarkers with high sensitivity, specificity, and accessibility for early detection, such as circulating microRNAs, is therefore of utmost importance. In the present study, we identified a significantly higher expression of miR-146a-5p in the serum and tissue samples of NSCLC patients than that of the healthy controls. In parallel, miR-146a-5p was also highly expressed in three human NSCLC adenocarcinoma-cell lines (A549, H1299, and H1975) compared to the human bronchial epithelium cell line (HBE). By dual-luciferase reporter assay and manipulation of the expressions of miR-146a-5p and its target gene, tumor necrosis factor receptor-associated factor 6 (TRAF6), we showed that the functional effects of miR-146a-5p on NSCLC cell survival and migration were mediated by direct binding to and suppression of TRAF6. Overexpression of TRAF6 sufficiently reversed miR-146a-5p-induced cancer cell proliferation, migration, and apoptosis resistance. Our data implied that miR-146a-5p/TRAF6/NF-κB-p65 axis could be a promising diagnostic marker and a therapeutic target for NSCLC.