CircMEMO1 modulates the promoter methylation and expression of TCF21 to regulate hepatocellular carcinoma progression and sorafenib treatment sensitivity.
CircMEMO1 modulates the promoter methylation and expression of TCF21 to regulate hepatocellular carcinoma progression and sorafenib treatment sensitivity.
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DOI：
10.1186/s12943-021-01361-3
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发表时间：
2021-05-13
期刊：
影响因子：
37.3
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Dong ZR;Ke AW;Li T;Cai JB;Yang YF;Zhou W;Shi GM;Fan J
肝硬化是一种公认的发展为肝细胞癌（HCC）的危险因素。很少有研究报道了与瘤旁异型增生结节（DN）样品相比，HCC样品中circRNA的表达谱。使用Arraystar Human circRNA Array与激光捕获显微切割（LCM）相结合来分析HCC样品中circRNA与癌旁DN样品相比的表达谱。然后，使用体外和体内HCC模型来确定关键circRNA在HCC进展和治疗敏感性中的作用和机制。我们发现circMEMO 1在HCC样本中显著下调，并且circMEMO 1的水平与HCC患者的OS和无病生存期（DFS）密切相关。机制分析显示，circMEMO 1可以调节TCF 21的启动子甲基化和基因表达，从而通过充当miR-106 b-5 p的海绵来调节HCC进展，miR-106 b-5 p靶向泰特家族基因并增加5 hmC水平。更重要的是，circMEMO 1可以增加HCC细胞对索拉非尼治疗的敏感性。我们的研究确定circMEMO 1可以促进TCF 21的去甲基化和表达，并且可以被认为是HCC进展中的关键表观遗传修饰因子。在线版本包含补充材料，可通过10.1186/s12943-021-01361-3获得。
Cirrhosis 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. The 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. We 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. Our study determined that circMEMO1 can promote the demethylation and expression of TCF21 and can be considered a crucial epigenetic modifier in HCC progression. The online version contains supplementary material available at 10.1186/s12943-021-01361-3.
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影响因子：
3.9
作者：
Dong ZR;Zou J;Sun D;Shi GM;Ke AW;Cai JB;Sun HC;Qiu SJ;Li T;Zhou J;Zhi XT;Fan J
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DOI：
10.1158/1078-0432.ccr-17-1958
发表时间：
2018-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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影响因子：
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