Circular RNA hsa_circ_0091579 facilitates the Warburg effect and malignancy of hepatocellular carcinoma cells via the miR-624/H3F3B axis

Abstract

Background: Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. It has been reported that circular RNA hsa_circ_0091579 (circ_0091579) is involved in HCC progression. Nevertheless, the molecular mechanism by which circ_0091579 modulates HCC advancement is indistinct. Methods: The expression of circ_0091579, microRNA (miR)-624, and H3 histone family member 3B (H3F3B) mRNA was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of HCC cells were analyzed using an extracellular flux analyzer. Adenosine triphosphate (ATP) level was evaluated using a commercial kit. Cell migration, invasion, and apoptosis were assessed by wound-healing, transwell, or flow cytometry assay. The relationship between miR-624 and circ_0091579 or H3F3B was verified using luciferase reporter assay and/or RNA immunoprecipitation (RIP) assay. H3F3B protein level was detected by western blotting. Results: Circ_0091579 was upregulated in HCC tissues and cells. Circ_0091579 inhibition decreased xenograft tumor growth in vivo and repressed Warburg effect, migration, invasion, and induced apoptosis of HCC cells in vitro. MiR-624 was downregulated, while H3F3B was upregulated in HCC tissues and cells. Circ_0091579 acted as a miR-624 sponge and regulated H3F3B expression by adsorbing miR-624. MiR-624 inhibitor reversed circ_0091579 downregulation-mediated effects on the Warburg effect and malignant behaviors of HCC cells. H3F3B overexpression reversed the repressive impact of miR-624 mimic on the Warburg effect and malignancy of HCC cells. Conclusions: Circ_0091579 accelerated Warburg effect and tumor growth via upregulating H3F3B via adsorbing miR-624 in HCC, providing evidence to support the involvement of circ_0091579 in the progression of HCC.