A miR-199a/miR-214 Self-Regulatory Network via PSMD10, TP53 and DNMT1 in Testicular Germ Cell Tumor

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.