Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

Abstract

BACKGROUND:

Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms.

METHODS:

Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1).

RESULTS:

It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level.

CONCLUSION:

Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

• Authors: Jin Wang, Lei Zhou, Bingxin Chen, Zhuwen Yu, Jianglei Zhang, Zhe Zhang, Chenrui Hu, Yanjin Bai, Xiaokang Ruan, Shengjia Wang, Jun Ouyang, Airong Wu, Xin Zhao
• Journal: Journal of translational medicine (J Transl Med) Vol. 20 Issue 1 Pg. 58 (01 31 2022) ISSN: 1479-5876 [Electronic] England
• PMID: 35101080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• MIRN431 microRNA, human
• MicroRNAs
• RNA, Circular
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• ROCK1 protein, human
• rho-Associated Kinases

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Colonic Neoplasms (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• In Situ Hybridization, Fluorescence
• MicroRNAs (genetics)
• RNA, Circular (genetics)
• Zinc Finger E-box-Binding Homeobox 1 (genetics, metabolism)
• rho-Associated Kinases (genetics, metabolism)