Department of Urology, The First Hospital of China Medical University, Shenyang, China.
J Cell Mol Med. 2021 Feb;25(3):1759-1770. doi: 10.1111/jcmm.16284. Epub 2021 Jan 15.
Much progress has been made in understanding the mechanism of bladder cancer (BC) progression. Protein kinase C-α (PKCα) is overexpressed in many kinds of cancers. Additionally, PKCα is considered an oncogene that regulates proliferation, invasion, migration, apoptosis and cell cycle in multiple cancers. However, the mechanism underlying how these cellular processes are regulated by PKCα remains unknown. In the present study, we used PKCα siRNA to knock down PKCα gene expression and found that down-regulation of PKCα could significantly inhibit cell proliferation, migration and invasion and induce apoptosis and G1/S cell cycle arrest in vitro. Overexpression of PKCα promotes tumour growth in vivo. We applied cDNA microarray technology to detect the differential gene expression in J82 cells with PKCα knockdown and found that five key genes (BIRC2, BIRC3, CDK4, TRAF1 and BMP4) were involved in proliferation and apoptosis according to GO analysis and pathway analyses. Correlation analysis revealed a moderate positive correlation between PKCα expression and the expression of five downstream genes. BIRC2 and BIRC3 inhibit apoptosis, whereas CDK4, TRAF1 and BMP4 promote proliferation. Essentially, all five of these target genes participated in proliferation, and apoptosis was regulated by PKCα via the NF-kB signalling pathway.
在理解膀胱癌(BC)进展的机制方面已经取得了很大进展。蛋白激酶 C-α(PKCα)在许多癌症中过表达。此外,PKCα被认为是一种致癌基因,可调节多种癌症中的增殖、侵袭、迁移、凋亡和细胞周期。然而,PKCα 如何调节这些细胞过程的机制尚不清楚。在本研究中,我们使用 PKCα siRNA 敲低 PKCα 基因表达,发现下调 PKCα 可显著抑制细胞增殖、迁移和侵袭,并诱导体外凋亡和 G1/S 细胞周期停滞。PKCα 的过表达可促进体内肿瘤生长。我们应用 cDNA 微阵列技术检测 PKCα 敲低的 J82 细胞中的差异基因表达,根据 GO 分析和通路分析发现,有五个关键基因(BIRC2、BIRC3、CDK4、TRAF1 和 BMP4)参与增殖和凋亡。相关性分析显示 PKCα 表达与五个下游基因的表达呈中度正相关。BIRC2 和 BIRC3 抑制凋亡,而 CDK4、TRAF1 和 BMP4 则促进增殖。本质上,这五个靶基因都参与了增殖,而凋亡是通过 NF-κB 信号通路由 PKCα 调节的。