The Expression Of PTPRO Gene Was Regulated By MiR-17-92 Cluster

MicroRNAs (miRNAs) are family of small non-coding RNAs about 21～25nt that regulate gene expression by targeting mRNAs for translational repression or mRNA cleavage. Current studies show that miRNA genes have been implicated in a variety of important biological processes, including development, differentiation, apoptosis, fat metabolism and cancer. Clarifying the prediction of target gene and the molecular mechanisms of these miRNAs in the oncogenesis is important to consider miRNAs as potential therapeutic targets.One cluster of miRNAs, the mir-17–92 polycistron functions as an oncogene in human and other animal models. Mir-17–92 cluster comprises seven miRNAs (miR-17-5p, miR-17-3p, miR-18, miR-19a, miR-20, miR-19b-1 and miR-92-1) and resides in intron 3of the C13 or f25 gene at 13q31.3 Mir-17–92 functions as an oncogene in human and other animal models. Enforced expression of the mir-17–92 cluster acted with c-myc expression to accelerate tumor development in a mouse B-cell lymphoma model. A noticeable issue about the function of mir-17–92 is its relationship with E2F1. Two recent papers suggested an auto-regulatory feed-back loop between E2F factors and miRNAs from the mir-17–92 cluster.To date, many targets of mir-17–92 have been determined, including E2F1. Targetscan (http://genes.mit.edu/tscan/targetscanS.html) was used to screen mir-17–92 potentially targeting the 3′-UTR of human PTPRO. Human PTPRO is a member of the receptor-type protein tyrosine phosphatases (RPTPs). DNA hypermethylation-mediated silencing of PTPRO was reported in primary human tumors and cancer cell lines. In addition, PTPRO exhibits characteristics of a candidate tumor suppressor in human lung cancer. However, how PTPRO gene is regulated and what roles PTPRO plays have not been identified. We tested the responsiveness of the PTPRO promoter to E2F1. Our results shew that PTPRO are transcriptionally regulated by E2F1 and PTPRO is post-transcriptonally regulated by mir-17-92. These results indicated that PTPRO is a target of mir-17-92. PTPRO is simultaneously regulated by E2F1 and mir-17-92.