title: Knockdown of protein phosphatase magnesium-dependent 1 (PPM1D) through lentivirus-mediated RNA silencing inhibits colorectal carcinoma cell proliferation.
abstract: 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.
authors.affiliation: Department of General Surgery, Sheng Jing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China. qisusy@163.com.
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Yin
authors.forename: Zhaopeng
authors.initials: Z
authors.lastname: Yan
authors.forename: Yichao
authors.initials: Y
authors.lastname: Liang
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms; D059585:G1 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D000071636:Protein Phosphatase 2C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C