miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling
Xiangjie Huang, Sisi Xiao, Xinping Zhu, Yun Yu, Meng Cao, Xiaodong Zhang, Shaotang Li, Wangyu Zhu, Fengjiao Wu, Xiaohui Zheng, Libo Jin, Congying Xie, Xiaoying Huang, Peng Zou, Xiaokun Li, Ri Cui, Xiaokun Li, Ri Cui
Abstract
Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with the miR-196b-5p expression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.