title: A miR-199a/miR-214 self-regulatory network via PSMD10, TP53 and DNMT1 in testicular germ cell tumor.
abstract: It was previously demonstrated that microRNA-199a (miR-199a) was down-regulated in testicular germ cell tumor (TGCT) partially caused by hypermethylation of its promoter. miR-199a is encoded by two loci in the human genome, miR-199a-1 on chromosome (Chr) 19 and miR-199a-2 on Chr 1. Both loci encode the same miR-199a. Another microRNA, microRNA-214 (miR-214), also locates on Chr 1. Previous study revealed that it is co-transcribed with miR-199a-2. However, the biological significance of the co-expression of miR-199a and miR-214 remains largely unknown. In this study, we determined that miR-199a and miR-214 were concordantly expressed in NT2 cells and TGCT patient tissues. After 5-aza treatment, miR-199-3p/5p and miR-214 expression was significantly increased. Silencing of DNMT1with siRNA restored the expression of miR-199a and miR-214, accompanied by de-methylation of the promoters of miR-199a-1/2. TP53 down-regulated the expression of DNMT1 in NT2 cells and overexpression of TP53 restored the expression of miR-199-3p/5p and miR-214. In addition, silencing of PSMD10 up-regulated the expression of TP53, while miR-214 over-expression resulted in PSMD10 down-regulation and TP53 up-regulation. Collectively, our findings highlighted a miR-199a/miR-214/PSMD10/TP53/DNMT1 self-regulatory network, which might be a potential therapeutic target in the treatment of TGCT.
authors.affiliation: 1] The Chinese University of Hong Kong - Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [2] Department of Biological Science and Biotechnology, School of Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China.
authors.forename: Bi-Feng
authors.initials: BF
authors.lastname: Chen
authors.affiliation: The Chinese University of Hong Kong - Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yick-Keung
authors.initials: YK
authors.lastname: Suen
authors.affiliation: The Chinese University of Hong Kong - Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Gu
authors.affiliation: The Chinese University of Hong Kong - Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: The Chinese University of Hong Kong - Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wai-Yee
authors.initials: WY
authors.lastname: Chan
mesh_terms: D015153:Blotting, Western; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics*; D013737:Testis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C547397:MIRN214 microRNA, human; D035683:MicroRNAs; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C531408:mirn199 microRNA, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D046988:Proteasome Endopeptidase Complex