circPVT1 Inhibits the Proliferation and Aids in Prediction of the Prognosis of Bladder Cancer

Hongyi Zhou,1,* Xueping Cui,2,* Leilei Zhu,1 Zhuoqun Xu,1 Zhuo Wang,3 Jianfeng Shao4 1Department of Urology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, 214023, People’s Republic of China; 2Department of Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, Zhejiang Province, 323000, People’s Republic of China; 3Department of Geriatrics, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, 214023, People’s Republic of China; 4Department of Urology, Wuxi No. 2 People’s Hospital (Jiangnan University Medical Center), Wuxi, Jiangsu Province, 214023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfeng Shao; Zhuo Wang, Email jianfenguro@163.com; wangzhuoausten@163.comBackground: Circular RNA PVT1 (circPVT1) is aberrantly expressed in several cancers, but its functional role and clinical relevance in bladder urothelial carcinoma (BLCA) remain unknown. This study aimed to identify the expression level of circPVT1 in BLCA and investigated its functional relevance with BLCA progression both in vitro and in vivo.Methods: GEPIA, UALCAN, and OncoLnc were referred to presented data. Quantitative real-time PCR (qPCR) was used for the measurement of transnational expression of genes in BLCA specimens and cell lines. Immunohistochemistry (IHC) and fluorescence in situ hybridization analysis (FISH) assays were performed to detect HER2 amplification, Pearson’s correlation analysis to analyze the correlation between circPVT1 expression and clinical characteristics, Cox regression and K-M survival analyses to analyze prognostic factors. A nomogram was constructed for predicting prognosis. The proliferation of cells was measured by CCK-8 and colony formation assay, and the proliferation in vivo was evaluated using nude mouse models. qPCR was used to detect the expression of proliferation-related genes.Results: circPVT1 was but mRNA PVT1 was not significantly overexpressed in BLCA. A high circPVT1 expression was associated with a better survival and negative HER2, but not with age, gender, and T stage. circPVT1 was an independent prognostic factor for the overall survival of BLCA patients. Knocking down circPVT1 promoted BLCA proliferation in vitro and in vivo. Knocking down circPVT1 upregulated ERBB2, MKI67, and PCNA expression and downregulated TP53 expression, but exerted no influence on CCND1 and CCNB1 expression.Conclusion: circPVT1 is a tumor suppressor and novel prognostic biomarker for BLCA.Keywords: circPVT1, bladder cancer, biomarker, proliferation, HER2 amplification, BLCA