MicroRNA-mediated alteration of TET2 interaction network in myeloproliferative neoplasms

摘要

Myeloproliferative neoplasms (MPNs) constitute a type of proliferative and dysplastic myeloid tumors, which are frequently found in the elderly people. Although some kinds of gene mutations in MPNs have been studied, the biological mechanisms behind this disease are still not very clear. Researchers have found that MPN patients with TET2 mutations have low level of 5hmC. However, they do not give reasons why there is also low level of 5hmC in patients with wild-type TET2. The aim of this study is to investigate into the role of TET2 and its interacting proteins in MPN under the repression by microRNAs. MicroRNAs are short, endogenous, non-coding RNA molecules, which regulate the target genes expression. We hypothesize that microRNAs lead to low level of 5hmC by down-regulating the expression of TET2 and other proteins interacting with TET2 in MPN patients with wild-type TET2, which is similar to the function of TET2 mutations. Bioinformatics tools were performed in this study. There were 11 databases considered, only 3 of which predicted microRNAs binding to TET2. Moreover, 10 proteins were found to be associated with TET2 according to STRING database and their targeting miRNA predictions was compared with that of TET2. The hypothesis can be supported by he predicted simultaneous repression of DNMT-1 and TET2 by miR-152.