A miRNAs panel promotes the proliferation and invasion ofcolorectal cancer cells by targeting GABBR1.

Yang Longqiu,Luo Pengcheng,Zhang Peng,Fei Xuejie

doi:10.1002/cam4.760

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.

Highlights

Colorectal cancer is one of the most common malignant tumors which contribute to the fifth cause of tumor death rates in China [1, 2]
Our results showed that miR-106a/b, miR-20a/b, and miR-17 could enhance colorectal cancer cell proliferation and invasion
We uncovered that the miR-106a/b, miR-2 1a/b, miR-1 7 which were higher expressed in the colorectal cancer tissues than in normal tissues downregulated the GABBR1 expression to influence the proliferation and invasion of colorectal cancer

Summary

Introduction

Colorectal cancer is one of the most common malignant tumors which contribute to the fifth cause of tumor death rates in China [1, 2]. The incidence of colorectal cancer is nearly 5% and the 5-year survival rate ranges from 40% to 60% [3]. Many protein-coding genes are involved in the regulation of proliferation of colorectal cancer cells. Stromal cell-derived factor-1 (SDF-1) has been reported to be associated with metastases of human colorectal cancer and local tumor progression [4]. PKC Beta II is a tumor suppressor in colorectal cancer cells survival [5]. Downregulation of Rpt reduced colorectal cancer growth [6]. These studies showed that many protein-coding genes

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Conclusion