Yu Xiaojie, Zhang Yiqiang, Wu Binggen, Kurie Jonathan M, Pertsemlidis Alexander
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 USA.
Department of Cell Systems and Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 USA.
Mol Ther Oncolytics. 2019 Aug 6;14:288-298. doi: 10.1016/j.omto.2019.07.004. eCollection 2019 Sep 27.
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) and and that miR-195 represses the migration and invasion of NSCLC cells . However, the relationship between miR-195 and microtubule structure and function and whether miR-195 represses NSCLC metastasis remain unknown. We assessed the correlation between tumor levels of and patient survival, the effect of TUBB on drug response, and the effect of miR-195 on migration, invasion, and metastasis and . We found that miR-195 directly targets ; knockdown of sensitizes cells to MTAs, while overexpression confers resistance; high expression of 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 to repress migration and invasion and metastasis . 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.
化疗耐药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，miR-195调节NSCLC对微管靶向药物（MTA）的敏感性，并且miR-195抑制NSCLC细胞的迁移和侵袭。然而，miR-195与微管结构和功能之间的关系以及miR-195是否抑制NSCLC转移仍不清楚。我们评估了肿瘤水平与患者生存率之间的相关性、TUBB对药物反应的影响以及miR-195对迁移、侵袭和转移的影响。我们发现miR-195直接靶向；敲低使细胞对MTA敏感，而过度表达则赋予抗性；的高表达与肺腺癌患者较差的生存率相关；TUBB也受CHEK1调节，CHEK1已被证明可调节化疗耐药性；并且miR-195靶向以抑制迁移、侵袭和转移。我们的研究结果突出了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。 （注：原文中存在重复表述，翻译时保留了原文的重复情况）
