Circular RNA Circ-0003006 Promotes Hepatocellular Carcinoma Proliferation and Metastasis Through Sponging miR-542-3p and Regulating HIF-1A

Qiang Tu,1,2 Xiaoxiang You,1,2 Jun He,1,2 Xuguang Hu,1,2 Changji Xie,1,2 Guohui Xu1,2 1Department of Hepatobiliary Oncology Surgery, Jiangxi Cancer Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Oncology Interventional, Jiangxi Cancer Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Qiang TuDepartment of Hepatobiliary Oncology Surgery, Jiangxi Cancer Hospital of Nanchang University, No. 519, Beijing East Road, Nanchang, 330029, Jiangxi, People’s Republic of ChinaEmail perfectttqq@126.comIntroduction: Hepatocellular carcinoma (HCC) is one most common cancer types among gastrointestinal cancer over the world, while its underlying mechanisms remain unclear. CircRNA has been revealed to participate in multiple biological functions and contribute to various diseases’ progression.Methods: Bioinformatic analysis of the differently expressed circRNAs in the HCC tissues, then verified by real-time quantitative PCR (RT-qPCR) assay. We found that circ-0003006 was upregulated in the HCC tissues, the cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to confirm the cell location of circ-0003006. shRNA silence assay was used to knock down the expression of circ-0003006 in the HCC cells.Results: Cell account kit 8 (CCK-8) and transwell assay were revealed that circ-0003006 knockdown inhibited the proliferation and metastasis in HCC cells. The target miR‑542‑3p and target gene HIF-1A were predicted by bioinformatics analysis, then verified through biotinylated RNA pull-down and dual-luciferase reporter assays. The mechanism, circ-0003006, probably acted as a sponge of miR‑542‑3p and regulated HIF-1A levels in hepatocellular carcinoma cells. Moreover, HIF-1A overexpression abolished the effect of circ-0003006 inhibition on the progression of hepatocellular carcinoma cells. The subcutaneous tumor formation experiment indicated that circ-0003006 knockdown inhibited the HCC cell growth in vivo.Conclusion: Circ-0003006 was demonstrated to promote HCC progression in vitro and in vivo by sponging miR‑542‑3p to release the inhibition on HIF-1A.Keywords: circular RNA, circ-0003006, miR-542-3p, HIF-1A, hepatocellular carcinom