Zhou Hongyi, Cui Xueping, Zhu Leilei, Xu Zhuoqun, Wang Zhuo, Shao Jianfeng
Department of Urology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, 214023, People's Republic of China.
Department 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.
Pharmgenomics Pers Med. 2024 Jan 5;17:1-11. doi: 10.2147/PGPM.S427147. eCollection 2024.
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.
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.
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.
circPVT1 is a tumor suppressor and novel prognostic biomarker for BLCA.
环状RNA PVT1（circPVT1）在多种癌症中异常表达，但其在膀胱尿路上皮癌（BLCA）中的功能作用和临床相关性尚不清楚。本研究旨在确定circPVT1在BLCA中的表达水平，并在体外和体内研究其与BLCA进展的功能相关性。
参考GEPIA、UALCAN和OncoLnc提供的数据。采用定量实时PCR（qPCR）检测BLCA标本和细胞系中基因的转录表达。进行免疫组织化学（IHC）和荧光原位杂交分析（FISH）检测HER2扩增，采用Pearson相关分析分析circPVT1表达与临床特征之间的相关性，采用Cox回归和K-M生存分析分析预后因素。构建列线图预测预后。通过CCK-8和集落形成试验检测细胞增殖，并使用裸鼠模型评估体内增殖情况。采用qPCR检测增殖相关基因的表达。
circPVT1在BLCA中显著过表达，但mRNA PVT1未显著过表达。circPVT1高表达与较好的生存率和HER2阴性相关，但与年龄、性别和T分期无关。circPVT1是BLCA患者总生存的独立预后因素。敲低circPVT1可促进BLCA在体外和体内的增殖。敲低circPVT1可上调ERBB2、MKI67和PCNA的表达，下调TP53的表达，但对CCND1和CCNB1的表达无影响。
circPVT1是BLCA的肿瘤抑制因子和新型预后生物标志物。
