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.

中文翻译：

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CircMEMO1 调节 TCF21 的启动子甲基化和表达以调节肝细胞癌进展和索拉非尼治疗敏感性

肝硬化是公认的发展为肝细胞癌 (HCC) 的危险因素。与肿瘤旁发育不良结节 (DN) 样本相比，很少有研究报道 HCC 样本中 circRNA 的表达谱。Arraystar Human circRNA Array 与激光捕获显微切割 (LCM) 相结合，用于分析 HCC 样本与副肿瘤 DN 样本中 circRNA 的表达谱。然后，使用体外和体内 HCC 模型确定关键 circRNA 在 HCC 进展和治疗敏感性中的作用和机制。我们发现 HCC 样本中 circMEMO1 显着下调，并且 circMEMO1 的水平与 HCC 患者的 OS 和无病生存期 (DFS) 密切相关。机制分析表明，circMEMO1 可以调节 TCF21 的启动子甲基化和基因表达，通过充当 miR-106b-5p 的海绵来调节 HCC 进展，miR-106b-5p 靶向 TET 基因家族并增加 5hmC 水平。更重要的是，circMEMO1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 circMEMO1 可以促进 TCF21 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。