CircGPRC5A enhances colorectal cancer progress by stabilizing PPP1CA and inducing YAP dephosphorylation

作者全名："Chen, Zhenzhou; Li, Yidan; He, Kuan; Yang, Jianguo; Deng, Qican; Chen, Yajun; Fu, Zhongxue"

作者地址："[Chen, Zhenzhou; Deng, Qican; Chen, Yajun; Fu, Zhongxue] Chongqing Med Univ, Affiliated Hosp 3, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Li, Yidan] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, Chongqing, Peoples R China; [He, Kuan; Yang, Jianguo] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China"

通信作者："Fu, ZX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Gastrointestinal Surg, Chongqing, Peoples R China."

来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001115411700001

JCR分区：Q1

影响因子：11.3

年份：2023

卷号：42

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：circGPRC5A; Colorectal cancer; PPP1CA; UBA1; YAP

摘要："BackgroundWith the advancements in bioinformatic technology, an increasing number of circular RNAs (circRNAs) have been discovered and their crucial roles in the development and progression of various malignancies have been confirmed through multiple pathways. However, the specific mechanisms involving protein-binding circRNAs in colorectal cancer (CRC) remain largely unexplored.MethodsDifferential circRNA expression was assessed using a human circRNA microarray in five CRC tissue and paired normal samples. CircGPRC5A expression was then confirmed in the CRC tissues and paired normal samples using qRT-PCR. The biological function of circGPRC5A in CRC were studied in vitro and in vivo. Western blotting, fluorescence in situ hybridization, immunofluorescence, RNA pulldown, mass spectrometry, immunoprecipitation, quantitative phosphoproteomics, and RNA-binding protein immunoprecipitation assays were used to study circGPRC5A.ResultsOur analysis revealed that circGPRC5A expression was higher in CRC tissues compared to normal tissues and was associated with tumor size, tumor stage and lymph node status. CircGPRC5A promoted CRC cell proliferation, migration, and metastasis in vitro and in vivo. CircGPRC5A could stabilize PPP1CA protein by inhibiting the binding between UBA1 and PPP1CA, and increasing YAP dephosphorylation.ConclusionsOur study revealed that circGPRC5A plays an essential function in CRC progression by stabilizing PPP1CA protein and enhancing YAP dephosphorylation. CircGPRC5A could act as a novel and potential target for CRC."

基金机构："Chongqing Municipal Public Health Bureau, Chongqing People's Municipal Government; Experimental Research Center of the First Affiliated Hospital of Chongqing Medical University"

基金资助正文：We thank the Experimental Research Center of the First Affiliated Hospital of Chongqing Medical University for equipment and technical support.