CircMEMO1 modulates the promoter methylation and expression of TCF21 to regulate hepatocellular carcinoma progression and sorafenib treatment sensitivity

Molecular Cancer

Ya-fei Yang¹  Tao Li¹  Guo-Ming Shi²  Jia-Bing Cai²  Wei Zhou²  Ai-Wu Ke²  Jia Fan³  Zhao-Ru Dong⁴ 

[1] Department of General Surgery, Qilu Hospital, Shandong University, 250012, Jinan, China;Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 YiXue Yuan Road, 200032, Shanghai, China;Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, 200032, Shanghai, China;Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 YiXue Yuan Road, 200032, Shanghai, China;Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, 200032, Shanghai, China;Cancer Center, Institutes of Biomedical Sciences, Fudan University, 200031, Shanghai, China;Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 YiXue Yuan Road, 200032, Shanghai, China;Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, 200032, Shanghai, China;Department of General Surgery, Qilu Hospital, Shandong University, 250012, Jinan, China;

关键词: HCC;    Circ RNA;    miR-106b-5p;    TET;    TCF21;   

DOI  :  10.1186/s12943-021-01361-3

来源: Springer

【 摘 要 】

BackgroundCirrhosis is a recognized risk factor for developing hepatocellular carcinoma (HCC). Few studies have reported the expression profile of circRNAs in HCC samples compared to paratumour dysplastic nodule (DN) samples.MethodsThe Arraystar Human circRNA Array combined with laser capture microdissection (LCM) was used to analyse the expression profile of circRNAs in HCC samples compared to paratumour DN samples. Then, both in vitro and in vivo HCC models were used to determine the role and mechanism of key circRNA in HCC progression and treatment sensitivity.ResultsWe found that circMEMO1 was significantly downregulated in HCC samples and that the level of circMEMO1 was closely related to the OS and disease-free survival (DFS) of HCC patients. Mechanistic analysis revealed that circMEMO1 can modulate the promoter methylation and gene expression of TCF21 to regulate HCC progression by acting as a sponge for miR-106b-5p, which targets the TET family of genes and increases the 5hmC level. More importantly, circMEMO1 can increase the sensitivity of HCC cells to sorafenib treatment.ConclusionOur study determined that circMEMO1 can promote the demethylation and expression of TCF21 and can be considered a crucial epigenetic modifier in HCC progression.

【 授权许可】

CC BY