Huang Hai, Peng Jian, Yi Shijian, Ding Chengmin, Ji Wei, Huang Qiangsong, Zeng Suna
Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital Nanning 530199, China.
Hepatobiliary and Enteral Surgery Research Center, Xiangya Hospital of Central South University Changsha 410008, China.
Am J Transl Res. 2021 Jun 15;13(6):6076-6086. eCollection 2021.
Circular RNAs (circRNAs) have been reported to regulate the hepatocellular carcinoma (HCC) chemoresistance and tumor progression by regulating gene expression. However, the underlying molecular mechanisms of HCC sorafenib resistance regulated by circRNAs remain unclear. Here, higher expression of circUBE2D2 was directly associated with low survival rate in HCC patients. Functional experiments showed that circUBE2D2 promoted the glycolysis (Warburg effect) and sorafenib resistance in vitro, and knockdown of circUBE2D2 repressed the tumor growth in vivo. Mechanistically, circUBE2D2 was predominantly localized in the cytoplasm and sponged miR-889-3p, which in turn targeted the 3'-UTR of LDHA mRNA. Therefore, circUBE2D2 exerted an oncogenic role through miR-889-3p/LDHA axis. In conclusion, these findings demonstrate that circUBE2D2 accelerated the HCC glycolysis and sorafenib resistance via circUBE2D2/miR-889-3p/LDHA axis, which provides a novel approach for HCC treatment.
据报道，环状RNA（circRNAs）可通过调节基因表达来调控肝细胞癌（HCC）的化疗耐药性和肿瘤进展。然而，circRNAs调控HCC索拉非尼耐药性的潜在分子机制仍不清楚。在此，circUBE2D2的高表达与HCC患者的低生存率直接相关。功能实验表明，circUBE2D2在体外促进糖酵解（瓦伯格效应）和索拉非尼耐药性，而敲低circUBE2D2可在体内抑制肿瘤生长。机制上，circUBE2D2主要定位于细胞质并吸附miR-889-3p，而miR-889-3p反过来靶向LDHA mRNA的3'-UTR。因此，circUBE2D2通过miR-889-3p/LDHA轴发挥致癌作用。总之，这些发现表明circUBE2D2通过circUBE2D2/miR-889-3p/LDHA轴加速HCC糖酵解和索拉非尼耐药性，这为HCC治疗提供了一种新方法。
