Yang Shikun, Yu Fei, Ji Yang, Shen Yanjun, Lu Hao, Gao Yuan, Zhang Feng, Wang Xuehao, Zhang Chuanyong
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Front Oncol. 2022 Apr 21;12:878513. doi: 10.3389/fonc.2022.878513. eCollection 2022.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and characterized by high aggressiveness and extremely poor prognosis. Increasing evidence has suggested that circular RNAs (circRNAs), which are highly stable, play crucial roles in the progression of multiple malignancies. However, the roles of circRNAs in HCC remain elusive.
The expression patterns of circRNAs in HCC were identified by qRT-PCR. A series of functional experiments both and were used to determine the role of circERBIN in HCC proliferation. Bioinformatics and an RNA pulldown assay were used to identify potential downstream targets of circERBIN.
The expression of circERBIN was upregulated in HCC cell lines and tissues, which was predictive of a poor prognosis in HCC patients. Elevated circERBIN promoted G1/S transition of HCC cells, thus facilitating the proliferation and tumorigenesis of HCC cells. Mechanistic investigations revealed that circERBIN regulated HCC proliferation by acting as a sponge of miR-1263, which subsequently targeted cyclin dependent kinase 6 and controlled G1/S transition.
Taken together, these results determined that circERBIN functions as an important epigenetic regulator in HCC development, highlighting that circERBIN is a promising target for treatment of HCC.
肝细胞癌(HCC)是最常见的原发性肝癌,具有高侵袭性和极差的预后。越来越多的证据表明,高度稳定的环状RNA(circRNA)在多种恶性肿瘤的进展中起关键作用。然而,circRNA在HCC中的作用仍不清楚。
通过qRT-PCR鉴定HCC中circRNA的表达模式。一系列体内和体外功能实验用于确定circERBIN在HCC增殖中的作用。生物信息学和RNA下拉实验用于鉴定circERBIN的潜在下游靶点。
circERBIN在HCC细胞系和组织中的表达上调,这预示着HCC患者预后不良。circERBIN升高促进了HCC细胞的G1/S期转换,从而促进了HCC细胞的增殖和肿瘤发生。机制研究表明,circERBIN通过作为miR-1263的海绵发挥作用来调节HCC增殖,miR-1263随后靶向细胞周期蛋白依赖性激酶6并控制G1/S期转换。
综上所述,这些结果确定circERBIN在HCC发展中作为一种重要的表观遗传调节因子发挥作用,突出表明circERBIN是治疗HCC的一个有前景的靶点。