MiR-199a-5p Inhibits the Growth and Metastasis of Colorectal Cancer Cells by Targeting ROCK1

Abstract

Mounting evidence indicates that microRNAs play important roles in the development of various cancers. Aberrant expression of microRNA-199a-5p has been frequently reported in cancer studies; however, the mechanistic details of the role of microRNA-199a-5p in colorectal cancer still remain unclear. Our study aimed to explore the role of microRNA-199a-5p in colorectal cancer cells by targeting Rho-associated coiled coil-containing protein kinase 1. Here, we showed that microRNA-199a-5p was significantly downregulated in colorectal cancer cell lines and tissue samples and was associated with a poor prognostic phenotype. MicroRNA-199a-5p suppressed colorectal cancer cell proliferation, migration, and invasion and induced cell apoptosis. Moreover, we identified Rho-associated coiled coil-containing protein kinase 1 as the direct target of microRNA-199a-5p using luciferase and Western blot assays. Importantly, Rho-associated coiled coil-containing protein kinase 1 overexpression rescued the microRNA-199a-5p-induced suppression of proliferation, migration, and invasion of colorectal cancer cells. Furthermore, the overexpression of microRNA-199a-5p inhibited tumor growth and metastasis by inactivating the phosphoinositide 3-kinase/AKT and Janus kinase 1/signal transducing activator of transcription signaling pathways through downregulation of Rho-associated coiled coil-containing protein kinase 1. Altogether, microRNA-199a-5p/Rho-associated coiled coil-containing protein kinase 1 may be a potential therapeutic target for colorectal cancer therapy.

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

“…Notably, microRNA-21 increases the expression level of occludin via ROCK1 suppression and, thus, stabilizes the intestinal barrier [65]. On the other hand, ROCK1 overexpression is associated with colorectal cancer (CRC) [66,67]. Moreover, microRNA-148a and microRNA-21 inhibit DNA methyltransferase 1 (DNMT1) [68], an oncogene which is also overexpressed in CRC [69][70][71].…”

Modulation in the microRNA repertoire is responsible for the stage-specific effects of Akt suppression on murine neuroendocrine prostate cancer

“…On the other end, in hepatocellular carcinoma [35] and colorectal cancer [36] mir155-5p has demonstrated its ability to resist apoptosis and promotes cellular proliferation, respectively. Intriguingly, although mir199a-5p was found to suppress tumor growth from colorectal cancer cells [37] , papillary thyroid carcinoma [38] , triple-negative breast cancer [39] and proliferation of esophageal cancer cells [40] , its down-regulation was shown to promote prostate adenocarcinoma progression [41] . Furthermore, mir29b-3p has been shown to act as a tumor suppressor in glioblastoma where it can inhibit cell growth and induce apoptosis in vitro [42] .…”

Exosomes of pasteurized milk: potential pathogens of Western diseases

“…It is thus possible that milk exosome-mediated uptake of bovine miR-148a, which is identical with human miR-148a (mirbase.org), targets DNMT1 and thereby attenuates the action of this critical promoter of CRC initiation and progression. Increased expression of Rho-associated coiled coil-containing protein kinase 1 (ROCK1) also plays a key role in CRC pathogenesis [274,275], which as well is a direct target of miR-148a [276].…”