Exosomal Circ-ZNF652 Promotes Cell Proliferation, Migration, Invasion and Glycolysis in Hepatocellular Carcinoma via miR-29a-3p/GUCD1 Axis

• Main Authors: Li Y, Zang H, Zhang X, Huang G
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-08-01
• Series: Cancer Management and Research
• Subjects: hcc; exosome; circ-znf652; mir-29a-5p; gucd1
• Online Access: https://www.dovepress.com/exosomal-circ-znf652-promotes-cell-proliferation-migration-invasion-an-peer-reviewed-article-CMAR

Yuhui Li, Hongliang Zang, Xue Zhang, Guomin Huang Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun 130012, People’s Republic of ChinaCorrespondence: Guomin Huang Tel [phone]Email [e-mail]: Circular RNAs (circRNAs) play a crucial role in hepatocellular carcinoma (HCC) progression. However, the role of exosomal circRNAs in HCC is still largely unknown. We aimed to explore the function of exosomal circ-ZNF652 in HCC.Methods: The morphology and size of exosomes were examined by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The expression of circ-ZNF652, ZNF652 mRNA, microRNA-29a-3p (miR-29a-3p) and guanylyl cyclase domain containing 1 (GUCD1) mRNA was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CD63, CD81, hexokinase 2 (HK2) and GUCD1 were examined via Western blot assay. The stability of circ-ZNF652 was examined by RNase R digestion assay. Cell proliferation was analyzed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration and invasion were assessed by transwell assay. The glycolysis level was detected via specific kits. The association between miR-29a-3p and circ-ZNF652 or GUCD1 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A murine xenograft model was constructed to explore the effect of circ-ZNF652 in vivo.Results: Exosomal circ-ZNF652 was upregulated in HCC patients’ serums and HCC cells. Exosomal circ-ZNF652 could transfer to HCC cells, and circ-ZNF652 silencing suppressed HCC cell proliferation, migration, invasion and glycolysis. Circ-ZNF652 was a sponge of miR-29a-3p, and the inhibitory effect of circ-ZNF652 silencing on HCC cell progression was weakened by miR-29a-3p inhibitor. GUCD1 was a target gene of miR-29a-3p, and GUCD1 overexpression restored the effect of miR-29a-3p on HCC cell development. Moreover, circ-ZNF652 knockdown repressed tumor growth in vivo.Conclusion: Exosomal circ-ZNF652 contributes to HCC cell proliferation, migration, invasion and glycolysis by miR-29a-3p/GUCD1 axis.Keywords: HCC, exosome, circ-ZNF652, miR-29a-5p, GUCD1