CircZCCHC2 (hsa_circ_0000854) promotes hepatocellular carcinoma progression through modulating miR-936/BTBD7 axis and activating Rho/ROCK2 pathway

Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive and refractory cancers due to its high propensity to metastasize and the unavailability of efficacious treatments. Circular RNAs (circRNAs) participate in diverse biological activities in human cancers. Here, we detected the upregulation of a novel circRNA, circZCCHC2 (hsa_circ_0000854), in HCC samples and cells. The upregulation indicated an unfavorable prognosis in HCC patients. CircZCCHC2 accelerated cell growth and metastasis in vitro and tumorigenicity in vivo. Mechanistic investigations revealed that circZCCHC2 regulated BTBD7 expression by sponging miR-936. Moreover, the suppression of malignancy caused by circZCCHC2 knockdown could be sufficiently reversed by miR-936 inhibition. Additionally, the suppressed Rho/ROCK2 pathway conferred by circZCCHC2 knockdown could be restored by inhibiting miR-936 expression. Collectively, our findings reveal that circZCCHC2 plays an oncogenic role of in HCC progression by modulating the miR-936/BTBD7/Rho/ROCK2 pathway.

Keywords

• Hepatocellular carcinoma
• circZCCHC2
• miR-936/BTBD7 axis
• Tumorigenesis
• Metastasis