Cancer Management and Research (Dec 2020)
CircPVT1 Regulates Cell Proliferation, Apoptosis and Glycolysis in Hepatocellular Carcinoma via miR-377/TRIM23 Axis
Abstract
Nan Bu,1,* Zheng Dong,2,* Lingfeng Zhang,3 Weibo Zhu,4 Furong Wei,5 Sheng Zheng6 1Department of Gastroenterology, Chinese Medicine Hospital of Jiamusi City, Heilongjiang Province, Jiamusi, Heilongjiang, People’s Republic of China; 2Department of General Surgery, Ningbo Mingzhou Hospital, Ningbo, Zhejinag, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First People’s Hospital of Huaihua City, Huaihua, Hunan, People’s Republic of China; 4Department of Medical Technology, Qujing Medical College, Qujing, Yunan, People’s Republic of China; 5Department of Gastroenterology, Central Hospital of Haining, Haining, Zhejinag, People’s Republic of China; 6Department of Gastroenterology, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sheng ZhengDepartment of Gastroenterology, The Third People’s Hospital of Yunnan Province, 292 Beijing Road, Guandu District, Kunming City, Yunnan Province, People’s Republic of ChinaTel +86-871-63196247Email [email protected]: Recent studies reported that circular RNAs (circRNAs) exert essential functions in hepatocellular carcinoma (HCC) progression. However, the expression profile and function of circular RNA PVT1 (circPVT1) in HCC are not fully addressed. Thus, we aimed to probe into the function of circPVT1 in HCC development.Methods: The levels of circPVT1, microRNA-377 (miR-377) and transcripts encoding tripartite motif containing 23 (TRIM23) were determined by qRT-PCR. The stability and localization of circPVT1 were examined by RNase R digestion assay and subcellular fraction assay, respectively. Cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The relationship between miR-377 and circPVT1 or TRIM23 was determined by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). The protein expression of TRIM23 was measured by Western blot. The glycolysis level was assessed by specific kits and Seahorse Extracellular Flux Analyzer XF96. The function of circPVT1 in vivo was investigated in a murine xenograft model.Results: CircPVT1 and TRIM23 levels were elevated, while miR-377 was decreased in HCC. CircPVT1 knockdown restrained proliferation and glycolysis, but enhanced apoptosis in HCC cells. CircPVT1 could bind to miR-377 and inhibition of miR-377 restored circPVT1 knockdown-mediated effect on HCC cells. TRIM23 was certified as a target of miR-377, and TRIM23 upregulation overturned the influence of miR-377 upregulation or circPVT1 silence on HCC progression. Moreover, circPVT1 knockdown restrained tumor growth in HCC in vivo.Conclusion: CircPVT1 aggravated the progression of HCC by upregulating TRIM23 via sponging miR-377.Keywords: hepatocellular carcinoma, circPVT1, miR-377, TRIM23
