Department of Cardiology, Tianjin First Central Hospital, Tianjing 300192, P.R. China.
Aging (Albany NY). 2020 Jun 17;12(12):12160-12174. doi: 10.18632/aging.103386.
Rho-associated kinase 1 (ROCK1) regulates tumor metastasis by maintaining cellular cytoskeleton homeostasis. However, the precise role of ROCK1 in non-small-cell lung cancer (NSCLC) apoptosis remains largely unknown. In this study, we examined the function of ROCK1 in NSCLS survival using RNA interference-mediated knockdown. Our results showed that ROCK1 knockdown reduced A549 lung cancer cell viability . It also inhibited A549 cell migration and proliferation. Transfection of ROCK1 siRNA was associated with increased expression of large tumor suppressor kinase 2 (LATS2) and c-Jun N-terminal kinase (JNK). Moreover, ROCK1 knockdown-induced A549 cell apoptosis and inhibition of proliferation were suppressed by LATS2 knockdown or JNK inactivation, suggesting that ROCK1 deficiency triggers NSCLC apoptosis in a LATS2-JNK pathway-dependent manner. Functional analysis further demonstrated that ROCK1 knockdown dysregulated mitochondrial dynamics and inhibited mitochondrial biogenesis. This effect too was reversed by LATS2 knockdown or JNK inactivation. We have thus identified a potential pathway by which ROCK1 downregulation triggers apoptosis in NSCLC by inducing LATS2-JNK-dependent mitochondrial damage.
Rho 相关激酶 1（ROCK1）通过维持细胞细胞骨架稳态来调节肿瘤转移。然而，ROCK1 在非小细胞肺癌（NSCLC）细胞凋亡中的精确作用在很大程度上仍不清楚。在这项研究中，我们使用 RNA 干扰介导的敲低来检查 ROCK1 在 NSCLS 存活中的功能。我们的结果表明，ROCK1 敲低降低了 A549 肺癌细胞的活力。它还抑制了 A549 细胞的迁移和增殖。ROCK1 siRNA 的转染与大肿瘤抑制激酶 2（LATS2）和 c-Jun N-末端激酶（JNK）的表达增加有关。此外，ROCK1 敲低诱导的 A549 细胞凋亡和增殖抑制被 LATS2 敲低或 JNK 失活所抑制，表明 ROCK1 缺乏以 LATS2-JNK 通路依赖性方式引发 NSCLC 细胞凋亡。功能分析进一步表明，ROCK1 敲低扰乱了线粒体动力学并抑制了线粒体生物发生。这种效应也被 LATS2 敲低或 JNK 失活所逆转。因此，我们已经确定了一种潜在的途径，即 ROCK1 下调通过诱导 LATS2-JNK 依赖性线粒体损伤来触发 NSCLC 细胞凋亡。
