Department of General Surgery, Sheng Jing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
Technol Cancer Res Treat. 2013 Dec;12(6):537-43. doi: 10.7785/tcrt.2012.500349. Epub 2013 Jun 6.
Colorectal cancer is one of the most common cancers in the world. Protein phosphatase magnesium-dependent 1 d (PPM1D) is aberrantly upregulated in many human carcinoma cells, and recent research has suggested that it could be a potential therapeutic target of cancer. However, the function of PPM1D in colorectal carcinoma cells is not well studied. To investigate the function of PPM1D in colorectal carcinoma, we used lentivirus-based RNA silencing to knock down the expression of PPM1D in RKO cells. We found that the lentivirus-mediated RNAi system efficiently decreased the expression level of endogenous PPM1D. Inhibiting PPM1D expression efficiently inhibited the proliferation and colony formation of RKO cells. Moreover, we found that PPM1D silencing led to G0/G1 cell-cycle arrest and the accumulation of cells at the sub-G1 phase. Furthermore, we found that PPM1D knockdown reduced the expression level of cyclinB1, inhibited ERK phosphorylation and activated the AKT signaling pathway. We found that PPM1D plays a crucial role in colorectal carcinoma cell proliferation and colony formation. Our work provides strong evidence suggesting that PPM1D is a potential therapeutic target of human colorectal cancers. Lentivirus-mediated PPM1D silencing is a promising gene therapeutic method to treat colorectal cancers.
结直肠癌是世界上最常见的癌症之一。蛋白磷酸酶镁依赖性 1d（PPM1D）在许多人类癌细胞中异常上调，最近的研究表明它可能是癌症的一个潜在治疗靶点。然而，PPM1D 在结直肠癌细胞中的功能尚未得到很好的研究。为了研究 PPM1D 在结直肠癌中的功能，我们使用基于慢病毒的 RNA 干扰敲低了 RKO 细胞中 PPM1D 的表达。我们发现慢病毒介导的 RNAi 系统有效地降低了内源性 PPM1D 的表达水平。抑制 PPM1D 表达能有效抑制 RKO 细胞的增殖和集落形成。此外，我们发现 PPM1D 沉默导致 G0/G1 细胞周期停滞和亚 G1 期细胞积累。此外，我们发现 PPM1D 敲低降低了 cyclinB1 的表达水平，抑制了 ERK 磷酸化并激活了 AKT 信号通路。我们发现 PPM1D 在结直肠癌细胞增殖和集落形成中起着关键作用。我们的工作为 PPM1D 是人类结直肠癌潜在治疗靶点提供了有力证据。慢病毒介导的 PPM1D 沉默是治疗结直肠癌的一种有前途的基因治疗方法。
