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

Journal of Translational Medicine

Lei Zhou¹  Bingxin Chen²  Airong Wu²  Zhuwen Yu²  Yanjin Bai³  Chenrui Hu³  Xiaokang Ruan³  Shengjia Wang³  Zhe Zhang⁴  Jin Wang⁵  Xin Zhao⁶  Jianglei Zhang⁷  Jun Ouyang⁷ 

[1]Department of Gastroenterology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China

[2]Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China

[3]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

[4]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

[5]Department of General Surgery, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China

[6]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

[7]Department of General Surgery, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China

[8]Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China

[9]Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China

[10]Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, Suzhou, China

[11]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

[12]Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China

[13]Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China

[14]Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, Suzhou, China

[15]Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

关键词: circCSPP1;    miR-431;    Rho associated coiled-coil containing protein kinase 1;    Zinc finger E-box binding homeobox 1;    Colon cancer;    Cell cycle;    Epithelial-to-mesenchymal transition;   

DOI  :  10.1186/s12967-022-03240-x

来源: Springer

【 摘 要 】

BackgroundColon 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.MethodsBioinformatics 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).ResultsIt 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.ConclusionTaken 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.

【 授权许可】

CC BY