943 MicroRNA 135a Suppresses Lymph Node Metastasis Through Down-Regulation of ROCK1 in Early Gastric Cancer

Abstract

MicroRNAs (miRNAs) play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC) including lymph node (LN) metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage$IB, 35.0% vs. 12.8%, p = 0.045) and higher rate of LN metastasis (30.0% vs. 5.1%, p = 0.014) than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p = 0.042). Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.

MiR‐202 inhibits cell proliferation, invasion, and migration in breast cancer by targeting ROCK1 gene

“…ROCK1, a member of the Rho‐associated serine/threonine kinase family, could facilitate the actin cytoskeleton reorganization during motion . It was confirmed to be upregulated in various cancers, such as gastric cancer, osteosarcoma, and prostate cancer . ROCK1 was considered as an oncogene because it was an crucial element in promoting migration, invasion, and metastasis of cancer cells .…”

“…**P < 0.01 when compared with NC-1 group or NC-2 group, respectively metastasis of cancer cells. 25 In Vennin et al 28 research, one of their important discoveries was that short-term targeted inhibition of ROCK1 could improve the efficacy of chemotherapy and also could destroy collective movement as well as impaired metastasis of pancreatic cancer cells, which is an major breakthrough in the clinical treatment of pancreatic cancer, even other cancers. Wu et al 29 suggested that the expression level of ROCK1 was closely associated with lymph node metastasis degree and tumor node metastasis (TNM) stage of gastric cancer, which could be used as a biological marker to evaluate malignancy degree of gastric cancer and also could be used as a predictor of gastric cancer occurrence, development, and metastasis.…”

“…It was confirmed to be upregulated in various cancers, such as gastric cancer, osteosarcoma, and prostate cancer . ROCK1 was considered as an oncogene because it was an crucial element in promoting migration, invasion, and metastasis of cancer cells . In Vennin et al research, one of their important discoveries was that short‐term targeted inhibition of ROCK1 could improve the efficacy of chemotherapy and also could destroy collective movement as well as impaired metastasis of pancreatic cancer cells, which is an major breakthrough in the clinical treatment of pancreatic cancer, even other cancers.…”

Upregulation of miRNA-202 promotes apoptosis and inhibits migration of glioma cell line via downregulation of ROCK1 gene

“…ROCK1 is a member of the Rho-associated serine/ threonine kinase family and play an important role in cell movement through reorganization of actin cytoskeleton [34]. It has been reported that ROCK1 is overexpressed in different cancers including prostate cancer [35], osteosarcoma [36], and gastric cancer [37]. ROCK1 gene is implicated in metastasis, invasion, and migration of cancer cells and could be considered as an oncogene [37].…”

“…It has been reported that ROCK1 is overexpressed in different cancers including prostate cancer [35], osteosarcoma [36], and gastric cancer [37]. ROCK1 gene is implicated in metastasis, invasion, and migration of cancer cells and could be considered as an oncogene [37]. Recent researches reported that the upregulation of ROCK1 is associated with poor survival in various cancers [38,39].…”