Exosome-transported circHDAC1_004 Promotes Proliferation, Migration, and Angiogenesis of Hepatocellular Carcinoma by the miR-361-3p/NACC1 Axis

Background and Aims:Hepatocellular carcinoma(HCC)is among the most common malignant tumors globally.Circular RNAs(circRNAs),as a type of noncoding RNAs,reportedly participate in various tumor biological processes.However,the role of circHDAC1_004 in HCC remains unclear.Thus,we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC.Methods:Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect circHDAC1_004 expression(circ_0005339)in HCC.Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004.In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC.Herein,qRT-PCR,RNA immunoprecipitation,western blotting,and a luciferase reporter assay were used to explore the relationships among circHDAC1_004,miR-361-3p,and NACC1.Results:circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival.circHDAC1_004 promoted HCC cell proliferation,stemness,migration,and invasion.In addition,circHDAC1_004 upregulated human umbilical vein endothelial cells(HUVECs)and promoted angiogenesis through exosomes.circHDAC1_004 promoted NACC1 expression and stimulated the epithelialmesenchymal transition pathway by sponging miR-361-3p.Conclusions:We found that circHDAC1_004 overexpression enhanced the proliferation,stemness,and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes.Our findings may help develop a possible therapeutic strategy for HCC.