title: MicroRNA-296 is enriched in cancer cells and downregulates p21WAF1 mRNA expression via interaction with its 3' untranslated region.
abstract: MicroRNAs (miRNAs) are a class of noncoding small RNAs that act as negative regulators of gene expression. To identify miRNAs that may regulate human cell immortalization and carcinogenesis, we performed comparative miRNA array profiling of human normal and SV40-T antigen immortalized cells. We found that miR-296 was upregulated in immortalized cells that also had activation of telomerase. By an independent experiment on genomic analysis of cancer cells we found that chromosome region (20q13.32), where miR-296 is located, was amplified in 28/36 cell lines, and most of these showed enriched miR-296 expression. Overexpression of miR-296 in human cancer cells, with and without telomerase activity, had no effect on their telomerase function. Instead, it suppressed p53 function that is frequently downregulated during human cell immortalization and carcinogenesis. By monitoring the activity of a luciferase reporter connected to p53 and p21(WAF1) (p21) untranslated regions (UTRs), we demonstrate that miR-296 interacts with the p21-3'UTR, and the Hu binding site of p21-3'UTR was identified as a potential miR-296 target site. We demonstrate for the first time that miR-296 is frequently upregulated during immortalization of human cells and contributes to carcinogenesis by downregulation of p53-p21(WAF1) pathway.
authors: National Institute of Advanced Industrial Science & Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki - 305 8562, Japan.
authors: A-rum
authors: AR
authors: Yoon
authors: Ran
authors: R
authors: Gao
authors: Zeenia
authors: Z
authors: Kaul
authors: Il-Kyu
authors: IK
authors: Choi
authors: Jihoon
authors: J
authors: Ryu
authors: Jane R
authors: JR
authors: Noble
authors: Yoshio
authors: Y
authors: Kato
authors: Soichiro
authors: S
authors: Saito
authors: Takashi
authors: T
authors: Hirano
authors: Tetsuro
authors: T
authors: Ishii
authors: Roger R
authors: RR
authors: Reddel
authors: Chae-Ok
authors: CO
authors: Yun
authors: Sunil C
authors: SC
authors: Kaul
authors: Renu
authors: R
authors: Wadhwa
mesh_terms: D020413:3' Untranslated Regions; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C549871:MIRN296 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53