title: MicroRNA-339-5p inhibits colorectal tumorigenesis through regulation of the MDM2/p53 signaling.
abstract: Tumor suppressor p53 plays a central role in tumor suppression. To ensure its proper function, the levels and activity of p53 are under a tight regulation in cells. MicroRNAs are short non-coding RNAs that play an important role in regulation of gene expression. Recently, microRNA-339-5p has been reported to be frequently down-regulated in colorectal cancer, and furthermore, its down-regulation is associated with poor prognosis in cancer patients, which strongly suggests a tumor suppressive function of microRNA-339-5p in colorectal cancer. In this study, we found that microRNA-339-5p directly represses the expression of MDM2, a key negative regulator of p53, through binding to MDM2 3'-UTR in colorectal cancer cells. Through the down-regulation of MDM2, microRNA-339-5p increases p53 protein levels and functions, including p53 transcriptional activity and p53-mediated apoptosis and senescence in response to stress. Furthermore, microRNA-339-5p inhibits the migration and invasion of colorectal cancer cells and the growth of colorectal xenograft tumors in a largely p53-dependent manner. Our results highlighted an important role of microRNA-339-5p in suppression of colorectal tumorigenesis, and also revealed that regulating the p53 function is an important mechanism for microRNA-339-5p in tumor suppression.
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA; These auhors contributed equally to this work.
authors.forename: Cen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA; These auhors contributed equally to this work.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA; Department of Breast Surgery, Qilu Hospital, Shandong University, Ji'nan, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Meihua
authors.initials: M
authors.lastname: Lin
authors.forename: Saurabh V
authors.initials: SV
authors.lastname: Laddha
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA; Department of Breast Surgery, Qilu Hospital, Shandong University, Ji'nan, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Center for Systems Biology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Chang S
authors.initials: CS
authors.lastname: Chan
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis* / Q000235:genetics; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C543820:MIRN339 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2