Circular RNA circBNC2 facilitates glycolysis and stemness of hepatocellular carcinoma through the miR-217/high mobility group AT-hook 2 (HMGA2) axis Running title: CircBNC2/miR-217/HMGA2 axis in HCC

Abstract

Abstract Hepatocellular cancer (HCC) constitutes approximately 90% of primary liver carcinoma and is a major health threaten worldwide. CircBNC2 has been implicated in the progression of several cancers. However, its roles in carcinogenesis and glycolysis in HCC are still unclear. In this study, CircBNC2 and high mobility group AT-hook 2 (HMGA2) were highly expressed while miR-217 was poorly expressed in HCC tissues and cells. CircBNC2 upregulation was related to poor prognosis and TNM staging. CircBNC2 knockdown inhibited HCC progression. Moreover, CircBNC2 knockdown suppressed the levels of PCNA, HK2, and OCT4. Notably, circBNC2 functioned as a molecular sponge of miR-217 to up-regulate HMGA2 expression. The inhibitory effects of circBNC2 silence on the growth and stemness of HCC cells, and levels of PCNA, HK2 and OCT4 were aggravated by miR-217 overexpression, but neutralized by HMGA2 overexpression. Besides, Furthermore, circBNC2 silence blocked tumor growth through upregulating miR-217 and downregulating HMGA2, PCNA2, HK2 and OCT4 in vivo. Thus, the current data confirmed that CircBNC2 sponged miR-217 to up-regulate HMGA2 level, thereby contributing to HCC glycolysis and progression. These findings may present novel insight into the pathogenesis and treatment of HCC.