Frontiers in Cell and Developmental Biology (Sep 2020)

miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6

  • Xiangdong Liu,
  • Xiangdong Liu,
  • Xiangdong Liu,
  • Bo Liu,
  • Bo Liu,
  • Bo Liu,
  • Ruihua Li,
  • Fei Wang,
  • Fei Wang,
  • Fei Wang,
  • Ning Wang,
  • Ning Wang,
  • Ning Wang,
  • Maihe Zhang,
  • Maihe Zhang,
  • Maihe Zhang,
  • Yang Bai,
  • Yang Bai,
  • Yang Bai,
  • Jin Wu,
  • Jin Wu,
  • Jin Wu,
  • Liping Liu,
  • Liping Liu,
  • Liping Liu,
  • Dongyu Han,
  • Dongyu Han,
  • Dongyu Han,
  • Zhiguang Li,
  • Bin Feng,
  • Guangbiao Zhou,
  • Shujing Wang,
  • Shujing Wang,
  • Li Zeng,
  • Li Zeng,
  • Li Zeng,
  • Jian Miao,
  • Yiqun Yao,
  • Bin Liang,
  • Lin Huang,
  • Lin Huang,
  • Qi Wang,
  • Yingjie Wu,
  • Yingjie Wu,
  • Yingjie Wu,
  • Yingjie Wu,
  • Yingjie Wu

DOI
https://doi.org/10.3389/fcell.2020.00847
Journal volume & issue
Vol. 8

Abstract

Read online

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.

Keywords