Involvement of the epigenetic aberration of hypoxia inducible factor 2 (HIF2) in development of uterine leiomyoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861329
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Yamaguchi University
• Principal Investigator: MAEKAWA Ryo 山口大学, 医学部附属病院, 助教 (90598749)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: DNAメチル化 / NRG1 / 子宮筋腫 / EGR / HIF2

Outline of Final Research Achievements

To obtain master gene candidates that may have key roles in the development of uterine leiomyomas (ULs), we first performed network analysis by combining genome-wide mRNA expression data, protein-protein gene interaction network data and genome-wide DNA methylation data. Then we obtained 5 master gene candidates. Of 5 candidate genes, we focused on HIF2 and NRG1. In ULs, HIF2 expression is downregulated with DNA hypermethylation and NRG1 is upregulated with DNA hypermethylation. Force expression of NRG1 in uterine smooth muscle cells (UtSMCs) showed several signaling pathways such as TGF-beta signaling and Wnt/beta-catenin signaling, that has been shown to be upregulated in ULs. Knockdown of HIF2 was not succeeded because the UtSMCs did not show enough levels of HIF2 expression. The results suggest that NRG1 is involved in the pathogenesis and development in ULs.

Free Research Field

医歯薬学