The miR-195 axis regulates chemoresistance through TUBB and lung cancer progression through BIRC5

Abstract Chemoresistance and metastasis are the major reasons for NSCLC treatment failure and patient deaths. We and others have shown that miR-195 regulates the sensitivity of NSCLC to microtubule-targeting agents (MTAs) in vitro and in vivo and that miR-195 represses the migration and invasion of NSCLC cells in vitro. However, the relationship between miR-195 and microtubule structure and function and whether miR-195 represses NSCLC metastasis in vivo remain unknown. We assessed the correlation between tumor levels of TUBB and patient survival, the effect of TUBB on drug response, and the effect of miR-195 on migration, invasion and metastasis in vitro and in vivo. We found that miR-195 directly targets TUBB, that knock-down of TUBB sensitizes cells to MTAs while over-expression confers resistance, that high expression of TUBB is correlated with worse survival of lung adenocarcinoma, that TUBB is also regulated by CHEK1, which has been shown to regulate chemoresistance, and that miR-195 targets BIRC5 to repress migration and invasion in vitro and metastasis in vivo. Our findings highlight the relevance of the miR-195/TUBB axis in regulating the response of NSCLC to MTAs and the importance of the miR-195/BIRC5 axis in regulating NSCLC metastasis.