Yin Jie, Zhang Guang-Cong, Fang Ying, Yu Xiang-Nan, Liu Tao-Tao, Dong Ling, Shen Xi-Zhong
Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
Shanghai Institute of Liver Diseases, Shanghai, China.
J Oncol. 2022 Mar 21;2022:5705896. doi: 10.1155/2022/5705896. eCollection 2022.
Evidence suggests that the role of senescence in the development of cancer is context-dependent. An orthologue of human pre-mRNA processing factor 19 (Prp19) attenuates the senescence of human endothelial cells. Prp19 has been reported to be involved in the progression of hepatocellular carcinoma (HCC). This work aims to investigate the effect of Prp19 on the senescence of HCC.
Senescence of L02 cells and HCC cells under different stimuli was detected through cell cycle analysis, SA--gal staining, and senescence associated secretory phenotype analysis. The relationship between Prp19 and senescence-related proteins was evaluated using real-time RT-PCR, western blot assay, and immunohistochemistry. Subcutaneous xenograft tumors in nude mice were used to evaluate the role of Prp19 on senescence . Data analysis was carried out using GraphPad Prism 6.
Prp19 facilitated the senescence of L02 cells and HCC cells under different stresses. Prp19 positively modulated p21 expression in the mRNA level. Downregulation of Prp19 promoted the growth of subcutaneous xenograft tumors generated by HCC cell lines.
Prp19 may promote senescence of HCC cells via regulating p21 expression.
有证据表明衰老在癌症发展中的作用取决于具体情况。人类前体mRNA加工因子19(Prp19)的一个直系同源物可减弱人类内皮细胞的衰老。据报道,Prp19参与肝细胞癌(HCC)的进展。这项研究旨在探究Prp19对HCC细胞衰老的影响。
通过细胞周期分析、SA-β-半乳糖苷酶染色及衰老相关分泌表型分析,检测不同刺激下L02细胞和HCC细胞的衰老情况。采用实时逆转录聚合酶链反应、蛋白质免疫印迹分析及免疫组织化学方法,评估Prp19与衰老相关蛋白之间的关系。利用裸鼠皮下异种移植瘤评估Prp19对衰老的作用。数据分析采用GraphPad Prism 6软件。
Prp19促进了不同应激条件下L02细胞和HCC细胞的衰老。Prp19在mRNA水平上正向调节p21的表达。Prp19的下调促进了HCC细胞系产生的皮下异种移植瘤的生长。
Prp19可能通过调节p21的表达促进HCC细胞的衰老。