Overexpression of miR-216b sensitizes NSCLC cells to cisplatin-induced apoptosis by targeting c-Jun

• Published in: Oncotarget 2017-11, Vol.8 (61), p.104206-104215
• Main Authors: Huang, Gang, Pan, Jiongwei, Ye, Zaiting, Fang, Bingmu, Cheng, Wei, Cao, Zhuo
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.22171

Platinum-based chemotherapy is still be the standard treatment for non-small cell lung cancer (NSCLC). Recently, studies demonstrate that some kinds of microRNAs (miRNAs) are associated with chemosensitivity of NSCLC cells to platinum-based treatment. Unfortunately, cancer cells usually change their expression profile of miRNAs to form drug resistance against chemotherapy. In the present study, we focused on miR-216b to investigate whether miR-216b determined sensitivity of NSCLC cells to cisplatin. We observed that expression level of miR-216b was significantly decreased in NSCLC cell lines when they were under the cisplatin treatment. However, restore of miR-216b by transfecting with its mimics was found to increase the cytotoxicity of cisplatin to NSCLC cells. Studies on mechanisms elucidated that miR-216b targeted c-Jun in NSCLC. Overexpression of miR-216b can suppress the cisplatin-induced upregulation of c-Jun. As the downstream, overexpression of Bcl-xl induced by c-Jun/ATF2 heterodimers was inhibited in miR-216b transfected NSCLC cells. Since Bcl-xl is a key anti-apoptotic protein, we found that sensitivity of NSCLC cells to cisplatin-induced apoptosis was significantly increased because of the overexpression of miR-216b.