Dysregulation of CircRNA_0001946 Contributes to the Proliferation and Metastasis of Colorectal Cancer Cells by Targeting MicroRNA-135a-5p

Zhenwei Deng; Xiyao Li; Huaiming Wang; Yongyong Geng; Yongchang Cai; Yuxin Tang; Yijun Wang; Xueqiao Yu; Libo Li; Ruiping Li

doi:10.3389/fgene.2020.00357

Dysregulation of CircRNA_0001946 Contributes to the Proliferation and Metastasis of Colorectal Cancer Cells by Targeting MicroRNA-135a-5p

Front Genet. 2020 May 8:11:357. doi: 10.3389/fgene.2020.00357. eCollection 2020.

Authors

Zhenwei Deng¹, Xiyao Li^{1

2}, Huaiming Wang³, Yongyong Geng⁴, Yongchang Cai¹, Yuxin Tang¹, Yijun Wang¹, Xueqiao Yu⁵, Libo Li¹, Ruiping Li¹

Affiliations

¹ Department of General Surgery, Dongguan People's Hospital, Southern Medical University, Dongguan, China.
² Department of General Surgery, The First Hospital of China Medical University, Shenyang, China.
³ Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Gastrointestinal Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁴ Department of Colorectal and Anal Surgery, Tumushuke People's Hospital, Tumushuke, China.
⁵ Department of Colorectal and Anal Surgery, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

This study was aimed to evaluate the potential function of circ-0001946 in the progression of colorectal cancer (CRC) and the related regulatory mechanism. First, the expression levels of circRNA_0001946 and microRNA-135a-5p (miR-135a-5p) in normal and CRC tissues were measured by quantitative real-time polymerase chain reaction (RT-qPCR). In addition, cell proliferation was assessed by the Cell Counting Kit-8 (CCK-8) assay, cell migration and invasion were evaluated by Transwell assays, and the cell cycle patterns were determined by flow cytometry. The relationship between the expression levels of circ_0001946 and miR-135a-5p was determined by dual-luciferase reporter assays. Our data showed that the expression of circ_0001946 was upregulated in CRC tissues, which was negatively correlated with tumor size, histologic grade, lymphatic metastasis, and TMN stage, and patients with circ_0001946 overexpression were more likely to have a poor prognosis. In addition, in vitro experiments showed that silencing circ_0001946 inhibited the epithelial-mesenchymal transition (EMT) pathway and markedly suppressed CRC cell growth, migration, and invasion. Furthermore, we discovered that the transfection of miR-135a-5p mimics could reverse the antitumor effects of circRNA_0001946 downregulation. To summarize, this study revealed that circRNA_0001946 might act as a tumor promoter by activating the miR-135a-5p/EMT axis and may be a promising treatment target for CRC.

Keywords: circRNA_0001946; colorectal cancer; metastasis; miR-135a-5p; proliferation.