Zhu Min, Liang Zi, Pan Jun, Zhang Xing, Xue Renyu, Cao Guangli, Hu Xiaolong, Gong Chengliang
School of Biology & Basic Medical Science, Soochow University, Suzhou 215123, China.
Mol Ther Nucleic Acids. 2021 Aug 19;25:668-682. doi: 10.1016/j.omtn.2021.08.011. eCollection 2021 Sep 3.
Hepatitis B virus (HBV) produces circular RNA (circRNA), whose functions have not yet been clearly elucidated. In this study, a novel circRNA HBV_circ_1 produced by HBV was identified in HBV-positive HepG2.2.15 cells and HBV-related hepatocellular carcinoma (HCC) tissue (HCCT). Microarray analysis of 68 HCCT samples showed that HBV_circ_1 abundance was significantly higher than that in paracancerous tissues. In addition, survival rate of HBV_circ_1-positive patients was significantly lower compared with HBV_circ_1-negative patients. Transient expression indicated that HBV_circ_1 enhanced cell proliferation, migration, and invasion and inhibited apoptosis . Furthermore, ectopical HBV_circ_1 expression increased tumor size . HBV_circ_1 was confirmed to interact with cyclin-dependent kinase 1 (CDK1) to regulate cell proliferation. These results suggest that HCC progression may be promoted by interaction of HBV_circ_1 with CDK1. Our data not only showed a novel clue to understand carcinogenesis and progress of HBV-related HCC but also provided a new target for the development of therapeutic drugs.
乙型肝炎病毒（HBV）产生环状RNA（circRNA），其功能尚未完全阐明。在本研究中，在HBV阳性的HepG2.2.15细胞和HBV相关的肝细胞癌（HCC）组织（HCCT）中鉴定出一种由HBV产生的新型circRNA HBV_circ_1。对68例HCCT样本的微阵列分析表明，HBV_circ_1丰度显著高于癌旁组织。此外，HBV_circ_1阳性患者的生存率显著低于HBV_circ_1阴性患者。瞬时表达表明，HBV_circ_1增强细胞增殖、迁移和侵袭，并抑制细胞凋亡。此外，异位表达HBV_circ_1会增加肿瘤大小。证实HBV_circ_1与细胞周期蛋白依赖性激酶1（CDK1）相互作用以调节细胞增殖。这些结果表明，HBV_circ_1与CDK1的相互作用可能促进HCC进展。我们的数据不仅为理解HBV相关HCC的致癌机制和进展提供了新线索，也为治疗药物的开发提供了新靶点。
