title: p55PIK transcriptionally activated by MZF1 promotes colorectal cancer cell proliferation.
abstract: p55PIK, regulatory subunit of class IA phosphatidylinositol 3-kinase (PI3K), plays a crucial role in cell cycle progression by interaction with tumor repressor retinoblastoma (Rb) protein. A recent study showed that Rb protein can localize to the mitochondria in proliferative cells. Aberrant p55PIK expression may contribute to mitochondrial dysfunction in cancer progression. To reveal the mechanisms of p55PIK transcriptional regulation, the p55PIK promoter characteristics were analyzed. The data show that myeloid zinc finger 1, MZF1, is necessary for p55PIK gene transcription activation. ChIP (Chromatin immuno-precipitation) assay shows that MZF1 binds to the cis-element "TGGGGA" in p55PIK promoter. In MZF1 overexpressed cells, the promoter activity, expression of p55PIK, and cell proliferation rate were observed to be significantly enhanced. Whereas in MZF1-silenced cells, the promoter activity and expression of p55PIK and cell proliferation level was statistically decreased. In CRC tissues, MZF1 and p55PIK mRNA expression were increased (P = 0.046, P = 0.047, resp.). A strong positive correlation (Rs = 0.94) between MZF1 and p55PIK mRNA expression was observed. Taken together, we concluded that p55PIK is transcriptionally activated by MZF1, resulting in increased proliferation of colorectal cancer cells.
authors.affiliation: Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Guihua
authors.initials: G
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jin
authors.forename: Xuelai
authors.initials: X
authors.lastname: Luo
authors.forename: Xianmin
authors.initials: X
authors.lastname: Xia
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
authors.forename: Junbo
authors.initials: J
authors.lastname: Hu
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human