环状ASPH通过HAO2的甲基化和表达促进肝细胞癌进展。

Zhuo Han, Xia Jinguo, Zhang Jin, Tang Junwei, Han Sheng, Zheng Qitong, Zhu Deming, Zhang Feihong, Xu Zhenggang, Sun Dongwei, Tan Zhongming, Wu Chen

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

School of Medicine, Jiangsu University, Zhenjiang, China.

Front Oncol. 2022 Jun 20;12:911715. doi: 10.3389/fonc.2022.911715. eCollection 2022.

CircRNAs have been reported to be related to hepatocellular carcinoma (HCC) development. Limited studies have revealed the expression profile of circRNAs in tumor and para-tumor normal samples in HCC patients. We found that circASPH was significantly increased in HCC tumor samples and that the level of circASPH was closely related to the overall survival of HCC patients. Mechanistically, circASPH could regulate the methylation of the promoter and expression of hydrocyanic oxidase 2 (HAO2) to promote HCC progression by acting as a sponge for miR-370-3p, and miR-370-3p could target DNMT3b and increase the 5mC level. In summary, our study determined that circASPH could regulate the methylation and expression of HAO2 and it could be considered an important epigenetic regulator in HCC progression.

据报道，环状RNA（circRNAs）与肝细胞癌（HCC）的发展有关。有限的研究揭示了HCC患者肿瘤及癌旁正常样本中circRNAs的表达谱。我们发现，circASPH在HCC肿瘤样本中显著升高，且circASPH水平与HCC患者的总生存期密切相关。机制上，circASPH可通过作为miR-370-3p的海绵，调节启动子的甲基化和氢氰酸氧化酶2（HAO2）的表达，从而促进HCC进展，而miR-370-3p可靶向DNMT3b并增加5mC水平。总之，我们的研究确定circASPH可调节HAO2的甲基化和表达，其可被视为HCC进展中的一种重要表观遗传调节因子。