MiR-195 potentiates the efficacy of microtubule-targeting agents in non-small cell lung cancer. (28th July 2018)

• Record Type: Journal Article
• Authors: Yu, Xiaojie; Zhang, Yiqiang; Ma, Xiuye; Pertsemlidis, Alexander
• Is Part Of: Cancer letters. Volume 427(2018)
• Page Start: 85
• Page End: 93
• Publication Date: 2018-07-28
• Subjects: miR-195 -- CHEK1 -- Non-small cell lung cancer -- Paclitaxel -- Eribulin; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.04.007
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Microtubule-targeting agents (MTAs) are widely used for the treatment of non-small cell lung cancer (NSCLC). The response rate is only ∼25%, mainly attributable to drug resistance. To identify determinants of resistance in NSCLC, we performed a high-throughput screen using a library of miRNA mimics. Here we report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and that repression of miR-195 confers resistance to MTAs. We show that NSCLC tumors over-expressing miR-195 are more sensitive to MTA treatment and that induced expression of miR-195 in NSCLC tumors potentiates the anti-tumor effect of MTAs. Additionally, we demonstrate that miR-195 targets checkpoint kinase 1 (CHEK1) to regulate the response of NSCLC cells to MTAs, that over-expression of CHEK1 contributes to resistance to MTAs and that knock-down of CHEK1 synergizes with MTAs to repress cell growth. Our results highlight the importance of miR-195 in regulating the response of NSCLC cells to MTAs and underline the potential application of miR-195 as a biomarker for response to MTAs, and as a therapeutic adjuvant to MTA treatment. Highlights: miR-195 sensitizes non-small cell lung cancer (NSCLC) to microtubule-targeting agents in vitro and in vivo. Repression of miR-195 contributes to resistance of NSCLC to MTAs in vitro. miR-195 regulates the response of NSCLC to MTAs by targeting checkpoint kinase 1 (CHEK1).