Identification of the upstream regulatory genes specific to the subtypes of uterine leiomyoma without the MED12 mutation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09262
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yamaguchi University
• Principal Investigator: SATO Shun 山口大学, 大学院医学系研究科, 助教 (10534604)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 子宮筋腫 / MED12突然変異 / 筋腫サブタイプ

Outline of Final Research Achievements

To clarify the specificity and commonality between the MED12-mut and MED12-wt uterine leiomyoma subtypes, based on the mRNA expression data, the aberrant expressed genes in each leiomyoma subtype and the co-expressed genes by the weighted gene co-expression network analysis were identified. The pathway analysis for the identified aberrant expressed genes and co-expressed genes revealed that the signaling pathways involving the extracellular matrix production and the angiogenesis are activated, in MED12-mut and MED12-wt leiomyoma subtypes, respectively. In addition, SATB2 and NRG1, which are involved in the onset and development of MED12-mut leiomyomas, are also highly expressed in the most MED12-wt leiomyoma specimens, suggesting that these genes may function in common in both leiomyoma subtypes. The findings in the study will be the basis for providing appropriate treatments for the patients bearing each leiomyoma subtype.

Free Research Field

分子生物学・産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

現在，子宮筋腫の根治には子宮摘出等の外科的手術が必要であり，子宮温存に有効な治療薬が求められている。効果が期待される治療薬の1つにプロゲステロン受容体調節剤があるが，既に実用化されている欧米では効果に個人差が報告されており，この効果の差異に個人が有する筋腫の種類（MED12(+)筋腫あるいはMED12(-)筋腫）が関与する可能性がある。本研究の成果であるMED12(+)筋腫とMED12(-)筋腫の特異性および共通性の知見は，患者の有する筋腫の種類により子宮温存を考慮した適切な治療を提供するための基礎となるので，少子化問題を抱える本邦にとっては社会的にも意義が大きい。