title: Post-transcriptional regulation of the tumor suppressor p53 by a novel miR-27a, with implications during hypoxia and tumorigenesis.
abstract: The tumor suppressor protein p53 is intricately regulated by various signaling molecules, including non-coding small RNAs, called microRNAs (miRNAs). The in silico analysis and the inverse expression status in various cell lines raised the possibility of miR-27a being a new regulator of p53. Using luciferase reporter assay and various mutational and functional analysis, we identified two putative binding sites of miR-27a on the 3'-UTR of p53. The overexpression of miR-27a in the human colorectal cancer cell line HCT-116+/+resulted in the decreased expression of the endogenous p53 protein levels. During hypoxia of the HCT-116+/+cells, p53 showed increased accumulation after 3 h, and the levels were significantly up-regulated until 24 h of hypoxia. The p53 expression dynamics during hypoxia of the HCT-116+/+cells were found to be inversely regulated by miR-27a expression. Moreover, using a cell viability assay, we established that after 3 h of hypoxia, the accumulation of p53 results in a decreased number of the viable HCT-116+/+cells and the overexpression of miR-27a resulted in an increased number of viable HCT-116+/+cells with a concomitant decrease in p53 expression. Additionally, our data indicated that miR-27a and p53 depict inverse expression dynamics in 50% of the human colorectal cancer samples studied, when compared with that in the adjacent normal samples. Our data established that miR-27a and the tumor suppressor protein p53 are part of the same signaling network that has important implications during hypoxia and tumorigenesis.
authors.affiliation: Department of Biotechnology, Hazratbal Srinagar, University of Kashmir, Jammu and Kashmir 190006, India.
authors.forename: Raihana
authors.initials: R
authors.lastname: Maqbool
authors.affiliation: Department of Biotechnology, Hazratbal Srinagar, University of Kashmir, Jammu and Kashmir 190006, India.
authors.forename: Saife Niaz
authors.initials: SN
authors.lastname: Lone
authors.affiliation: Department of Biotechnology, Hazratbal Srinagar, University of Kashmir, Jammu and Kashmir 190006, India.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Ul Hussain
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53
keywords: colorectal cancer; hypoxia; miR-27a; p53; tumor suppressor protein