Circular RNA circUBE2D2 functions as an oncogenic factor in hepatocellular carcinoma sorafenib resistance and glycolysis.
Hai Huang, Jian Peng, Shijian Yi, Chengmin Ding, Wei Ji, Qiangsong Huang, Suna Zeng
Abstract
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.