title: Altered p53 regulation of miR-148b and p55PIK contributes to tumor progression in colorectal cancer.
abstract: MicroRNAs are a class of small non-coding RNAs that regulate the expressions of many genes. Previously, we found that the expression of p55PIK, an isoform of phosphatidylinosotol 3-kinase that has important roles in the regulation of cell cycle, is increased significantly in several types of cancer and contributes to the tumor growth. However, the mechanism for this increased p55PIK expression is not well understood. In this study, we show that miR-148b binds specifically to the 3'-untranslated region of p55PIK and significantly suppresses p55PIK expression. MiR-148b overexpression abolished p55PIK stimulation of cell proliferation and cell cycle progression in colorectal cancer (CRC) cell lines and decreased tumor growth in vivo. Furthermore, we demonstrated that p53 directly activates the transcription of miR-148b by binding to its promoter. In CRC cell lines and tissues, p53 expression was associated with miR-148b expression, and both were negatively associated with p55PIK expression. Our study shows that the p53/miR-148b/p55PIK axis has an important role in cell proliferation and tumor growth, and may represent a novel therapeutic target for treating cancers containing p53 mutations or losses.
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: S
authors.initials: S
authors.lastname: Lai
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Gong
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
mesh_terms: D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human