Hu Jianwei, Xie Wenjuan, Shang Lingyue, Yang Xi, Li Quanlin, Xu Meidong, Dou Jianming, Zhou Yiren, Niu Weixin, Wu Yanhua
1 Endoscopy Center and Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, P.R. China.
2 State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, P.R. China.
Tumour Biol. 2017 Jul;39(7):1010428317706455. doi: 10.1177/1010428317706455.
Calponin family members are actin filament-associated regulatory proteins with distinct expression patterns. Previous studies on CNN2 (calponin 2) have demonstrated that CNN2 is expressed in a broad range of tissues and cell types, exhibiting potential regulatory roles in a number of cellular activities, including cell proliferation, cell migration, and platelet adhesion. In this work, we found that both messenger RNA and protein expression levels of CNN2 were remarkably upregulated in 60%-70% of gastric cancer tissues by comparison with those of neighboring non-tumorous mucosa. By utilizing specific shCNN2 (small hairpin RNA targeting CNN2), the potential role of CNN2 in regulating AGS gastric cancer cell growth was then further investigated. AGS cells infected with shCNN2 exhibited significantly decreased cell growth ability by comparison with control cells in vitro. Moreover, while there was no obvious difference in cell cycle distribution between two groups, enhanced cell apoptosis was detected in cells with reduced CNN2 expression. Consistently, caspase 3/7 activity was also remarkably activated upon shCNN2 lentivirus infection. Taken together, our results demonstrated that knockdown of endogenous CNN2 in AGS cells could significantly activate cell apoptosis pathway and therefore suppress cell growth in vitro. The deletion of CNN2 might be a potential therapeutic approach to inhibit aggressive growth of gastric cancer.
钙调蛋白家族成员是与肌动蛋白丝相关的调节蛋白,具有不同的表达模式。先前对CNN2(钙调蛋白2)的研究表明,CNN2在广泛的组织和细胞类型中表达,在许多细胞活动中发挥潜在调节作用,包括细胞增殖、细胞迁移和血小板黏附。在本研究中,我们发现与相邻的非肿瘤黏膜相比,60%-70%的胃癌组织中CNN2的信使核糖核酸和蛋白质表达水平均显著上调。通过使用特异性shCNN2(靶向CNN2的小发夹RNA),进一步研究了CNN2在调节AGS胃癌细胞生长中的潜在作用。与体外对照细胞相比,感染shCNN2的AGS细胞表现出显著降低的细胞生长能力。此外,虽然两组细胞周期分布没有明显差异,但在CNN2表达降低的细胞中检测到细胞凋亡增加。同样,在感染shCNN2慢病毒后,半胱天冬酶3/7活性也显著激活。综上所述,我们的结果表明,敲低AGS细胞中的内源性CNN2可显著激活细胞凋亡途径,从而在体外抑制细胞生长。CNN2的缺失可能是抑制胃癌侵袭性生长的一种潜在治疗方法。