Παρασκευή 27 Μαΐου 2016

A miRNAs panel promotes the proliferation and invasion of colorectal cancer cells by targeting GABBR1

Abstract

MicroRNAs (miRNAs) have been implicated in the regulation of colorectal cancer. Despite the expression of miR-17-92 cluster in cancer has been gradually revealed, the role of each individual miRNAs in colorectal cancer still remains unclear. We studied the impact of miR-106a/b, miR-20a/b, and miR-17 of miR-17-92 cluster on colorectal cancer cells. Real-time quantitative polymerase chain reactions (RT-PCR) were used to test these five miRNAs expression in colorectal cancer cell line HCT116. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays, Bromodeoxyuridine (BrdU), and Transwell invasion assays were used to explore the effects of these five miRNAs in colorectal cancer cells. Luciferase reporter assay, RT-PCR, and western blotting were performed to validate the interaction of these five miRNAs with the gamma-amino-butyric acid type B receptor 1(GABBR1). We found that these five miRNAs were significantly upregulated in colorectal cancer samples compared with normal tissues. Forced expression of these five miRNAs significantly promoted HCT116 and HT-29 cells proliferation and invasion. We further found that these five miRNAs function as oncogenes in colorectal cancer by specifically binding to the 3-untranslated regions (3′UTR) of GABBR1.Furthermore, inhibition of GABBR1 could mimic the function of miRNAs in HCT116 cells, while overexpression of GABBR1 blocked the function of miRNAs-promoted proliferation and invasion. In conclusion, miR-106a/b, miR-20a/b, and miR-17 contribute to the proliferation and invasion of colorectal cancer by targeting their common target gene, GABBR1, and played a critical role in the proliferation and invasion of colorectal cancer.

Thumbnail image of graphical abstract

We studied the impact of miR-106a/b, miR-20a/b, and miR-17 of miR-17-92 cluster on colorectal cancer cells. miR-106a/b, miR-20a/b, and miR-17 contribute to the proliferation and invasion of colorectal cancer by targeting their common target gene, GABBR1, and played a critical role in the proliferation and invasion of colorectal cancer.



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