CircATF6 inhibits hepatocellular carcinoma progression by suppressing calreticulin-mediated Wnt/β-catenin signaling pathway.

Autor: Wang YN; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China., Cao D; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China; Department of Medical Image, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China., Liu J; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China., Ren QN; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China., Weng NQ; Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China., Zhou YF; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China., Zhang MY; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China., Wang SC; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China., Chen MS; Department of Liver surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China. Electronic address: chenmsh@sysucc.org.cn., Mai SJ; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China. Electronic address: maishj@sysucc.org.cn., Wang HY; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China. Electronic address: wanghyun@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2024 Oct; Vol. 122, pp. 111298. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.cellsig.2024.111298
Abstrakt: Circular RNAs (circRNAs) are covalently closed, single-stranded RNAs that play critical roles in various biological processes and diseases, including cancers. However, the functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) need further clarification. Here, we identified and confirmed that circATF6 is downregulated in HCC tissues and negatively associated with the overall survival of HCC patients. Ectopic overexpression of circATF6 inhibits malignant phenotypes of HCC cells in vitro and in vivo, while knockdown of circATF6 had opposite effects. Mechanistically, we found that circATF6 bound to calreticulin (CALR) protein and acted as a scaffold to enhance the interaction of CALR with calpain2 (CAPN2), which promoted the degradation of CALR by its enzymatic activity. Moreover, we found that circATF6 inhibited HCC cells by suppressing CALR-mediated wnt/β-catenin signaling pathway. Taken together, our findings suggest that circATF6 is a potential prognostic biomarker and therapeutic target for HCC.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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