Circ-CSPP1 knockdown suppresses hepatocellular carcinoma progression through miR-493-5p releasing-mediated HMGB1 downregulation |
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| Affiliation: | 1. Department of Ophthalmology, The First People’s Hospital of Jinzhou (Yangtze University Affiliated First People’s Hospital), Hubei, 434000, PR China;2. Department of Oncology, Jingzhou Central Hospital, The Second Clinical Medical College of Yangtze University, Hubei, 434020, PR China;3. Department of Ophthalmology, Xiangyang Central Hospital, Hubei, 441021, PR China;1. Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Via F.Cervi 93, 20090, Segrate, Milan, Italy;2. Department of Pharmacological & Biomolecular Sciences (DiSFeB), University of Milan, Via Pascal 36, 20133, Milan, Italy;1. Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, No. 246 XueFu Avenue, Harbin 150086, China;2. Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Block T, Queen Mary Hospital, Pokfulam 999077, China;1. Department of Nephrology, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, Hubei, P.R. China;2. Department of Endocrinology, The First People''s Hospital of Lanzhou City, Lanzhou, Gansu, P.R. China;3. Department of Nephrology, Weifang People''s Hospital, Weifang, Shandong, P.R. China |
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| Abstract: | BackgroundHepatocellular carcinoma (HCC) accounts for over 80% of primary liver cancers and leads to a high death rate. Research on circular RNAs (circRNAs) suggests that circRNAs are promising biomarkers for cancer treatment. This study aimed to explore the function of a novel circRNA (circ-CSPP1) in HCC.MethodsCirc-CSPP1 was obtained from the microarray data downloaded from the Gene Expression Omnibus (GEO) database. The expression of circ-CSPP1, miR-493-5p and high mobility group box 1 (HMGB1) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation ability, migration and invasion were monitored using cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay and transwell assay, respectively. The protein levels of CyclinD1, Vimentin, matrix metallopeptidase 9 (MMP-9) and HMGB1 were detected by western blot. Xenograft models were established to investigate the function of circ-CSPP1 in vivo. The association between miR-493-5p and circ-CSPP1 or HMGB1 was predicted by the online tool starBase and ensured by dual-luciferase reporter assay.ResultsThe expression of circ-CSPP1 and HMGB1 was elevated, while the expression of miR-493-5p was declined in HCC tissues and cells. Circ-CSPP1 knockdown not only depleted HCC cell proliferation, formation, migration and invasion in vitro but also inhibited tumor growth in vivo. MiR-493-5p was a target of circ-CSPP1, and HMGB1 was a target of miR-493-5p. Rescue experiments presented that miR-493-5p deficiency reversed the effects of circ-CSPP1 knockdown, and HMGB1 overexpression reversed the effects of miR-493-5p restoration. Circ-CSPP1 sponged miR-493-5p to regulate HMGB1 expression.ConclusionKnockdown of circ-CSPP1 suppressed HCC development both in vitro and in vivo by upregulation of miR-493-5p and downregulation of HMGB1, hinting that circ-CSPP1 participated in HCC pathogenesis. |
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