Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072, Shanghai, China.
Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, China.
Cell Death Dis. 2018 Oct 25;9(11):1091. doi: 10.1038/s41419-018-1132-6.
Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the -1409 to -1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N-methyladenosine (mA) motif was identified in the 353-357 region of YAP 3'UTR, and this mA modification was essential for the interaction between miR-582-3p and YAP 3'UTR. Further, the diagnostic performance of circ_104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ_104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ_104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ_104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ_104075 may provide new strategies in HCC diagnosis and therapy.
某些类型的环状 RNA（circRNA）在包括肝细胞癌（HCC）在内的人类疾病中异常表达。然而，其调控机制和诊断作用在很大程度上仍是未知的。在这里，我们鉴定出环状 RNA_104075（circ_104075）在 HCC 组织、细胞系和血清中高表达。从机制上讲，HNF4a 与 circ_104075 启动子的-1409 至-1401 区域结合，以刺激 circ_104075 的表达。此外，circ_104075 作为 ceRNA 通过吸收 miR-582-3p 而上调 YAP 的表达。有趣的是，在 YAP 3'UTR 的 353-357 区域中鉴定出一个 N-甲基腺苷（mA）基序，并且这种 mA 修饰对于 miR-582-3p 和 YAP 3'UTR 之间的相互作用是必需的。此外，评估了 circ_104075 的诊断性能。circ_104075 的接收者操作特征（ROC）曲线下面积（AUC-ROC）为 0.973，灵敏度为 96.0%，特异性为 98.3%。总之，我们确定 circ_104075 在 HCC 中高度表达，并阐明了其上游和下游调控机制。circ_104075 还具有作为 HCC 新诊断生物标志物的潜力。靶向 circ_104075 可能为 HCC 的诊断和治疗提供新的策略。
