Chemoresistance and metastasis are the major reasons for non-small cell lung cancer (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; knockdown of TUBB sensitizes cells to MTAs, while overexpression confers resistance; high expression of TUBB is correlated with worse survival of lung adenocarcinoma; TUBB is also regulated by CHEK1, which has been shown to regulate chemoresistance; and 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.

化学耐药性和转移是非小细胞肺癌（NSCLC）治疗失败和患者死亡的主要原因。我们和其他人已经表明了miR-195调节的非小细胞肺癌对靶向微管的代理（MTA）的灵敏度在体外和在体内和了miR-195阻抑NSCLC细胞的迁移和侵袭体外。但是，miR-195与微管结构和功能之间的关系以及miR-195是否在体内抑制NSCLC转移仍是未知的。我们评估了TUBB肿瘤水平与患者生存率，TUBB对药物反应的影响以及miR-195对体外和体外迁移，侵袭和转移的影响之间的相关性。体内。我们发现miR-195直接靶向TUBB；TUBB的敲低使细胞对MTA敏感，而过表达则赋予抗性。TUBB的高表达与肺腺癌的生存期较差有关。TUBB还受CHEK1的调节，CHEK1已被证明可调节化学抗性。和miR-195靶向BIRC5来抑制体外迁移和侵袭以及体内转移。我们的发现突出了miR-195 / TUBB轴在调节NSCLC对MTA反应中的相关性，以及miR-195 / BIRC5轴在调节NSCLC转移中的重要性。