ROCK1 knockdown inhibits non-small-cell lung cancer progression by activating the LATS2-JNK signaling pathway

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.

Hsa_circ_0041268 promotes NSCLC progress by sponging miR‐214‐5p/ROCK1

“…ROCK1 knockdown inhibits NSCLC progression through activating the LATS2-JNK signaling pathway. 34 Our data found that hsa_circ_0041268 downregulation or miR-214-5p overexpression suppressed ROCK1 expression.…”

“…In prostate cancer, increased ROCK1 expression was an early biomarker of poor prognoses, because it was associated with the genetic instability of cancer cells. ROCK1 knockdown inhibits NSCLC progression through activating the LATS2‐JNK signaling pathway 34 . Our data found that hsa_circ_0041268 downregulation or miR‐214‐5p overexpression suppressed ROCK1 expression.…”

Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis

“…Additionally, whether circ_PIP5K1A could regulate the signaling pathways via the miR-493-5p/ROCK1 axis remains unknown. ROCK1 has inactivated the LATS2-JNK pathway and PTEN/PI3K/FAK pathway in NSCLC progression regulation [ 27 , 28 ]. Exploring the signaling pathways in the downstream of circ_PIP5K1A/miR-493-5p/ROCK1 will be beneficial for the better understanding of the functional mechanism behind circ_PIP5K1A.…”

LncRNA PITPNA-AS1 as a Potential Diagnostic Marker and Therapeutic Target Promotes Hepatocellular Carcinoma Progression via Modulating miR-448/ROCK1 Axis

“…ROCK1, a vital downstream effecting element pertaining to the small GTPase RhoA, refers to one serine/threonine kinase, mediating a range of cellular responding processes (e.g., cell proliferating process, growing process, and apoptosis based on microtubule network organizing process and influences on the cytoskeleton) (21). ROCK1 served as an oncogene, with the involvement inside different progressions (e.g., cell migrating process, metastasis, as well as invading process) (22,23). In HCC, it has been demonstrated that ROCK1 was overexpressed in HCC specimens and promoted the proliferation and metastasis of HCC cells (24)(25)(26)(27)(28).…”