Abstract
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 in vitro. 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.
Highlights
Non-small-cell lung cancer (NSCLC) is a main cause of cancer death worldwide and accounts for approximately 80–85% of all lung cancer cases [1]
A549 cells were transfected with siRNA against Rho-associated kinase 1 (ROCK1) in a loss-of-function assay, and large tumor suppressor kinase 2 (LATS2) expression and Jun N-terminal kinase (JNK) transcription were measured
A549 cells were transfected with siRNA against ROCK1 to observe the effects of ROCK1 in NSCLC development and progression
Summary
Non-small-cell lung cancer (NSCLC) is a main cause of cancer death worldwide and accounts for approximately 80–85% of all lung cancer cases [1]. Recent advances in diagnosis and treatment have improved the survival of patients with early stage NSCLC [2]. A growing number of studies have examined the molecular mechanisms of NSCLC carcinogenesis, they remain largely unknown. The mild symptoms and clinical signs that characterize earlystage NSCLC can preclude early detection, and NSCLC progresses rapidly. Most patients are diagnosed at advanced stages, resulting in poor prognosis and low survival rates [3]. Additional studies are needed to improve understanding of the pathogenesis and molecular mechanisms of NSCLC and to identify potential treatment targets to reduce NSCLC cell survival, invasion, and proliferation
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