A novel mechanism of endometrial cancer development involving microRNAs

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyushu University
• Principal Investigator: ASANOMA KAZUO 九州大学, 医学研究院, 准教授 (30380413)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: マイクロRNA / 上皮間葉移行 / 子宮体癌

Outline of Final Research Achievements

BHLHE40 and BHLHE41 (BHLHE40/41) are transcription factors involved in multiple cell activities including epithelial-to-mesenchymal transition (EMT). However, the expression mechanism of BHLHE40/41 in EMT remains unclear. In the present study, we showed that the expression levels of BHLHE40/41 were negatively correlated with those of the microRNA (MIR) 130 family in endometrial cancer (EC) specimens. Our in vitro assays indicated that the expression of BHLHE40/41 was suppressed directly by the MIR130 family in a 3’-untranslated region-mediated manner. In EC cells, the MIR130 family promoted EMT and tumor cell invasion by suppressing the expression of BHLHE40/41. We identified the critical promoter region of the MIR301B-MIR130B cluster for its basal transcription by SP1. We also found that BHLHE40/41 suppressed the expression of MIR301B and MIR130B, and we identified a binding site in the promoter region for BHLHE40/41.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

我々は子宮体癌の進展機序である上皮間葉移行においてBHLHE40/41とMIR130ファミリーとの互いの発現制御機構が関わることを世界で初めて見出した。BHLHE40/41とMIR130ファミリーは子宮体癌症例の進展を予測する分子マーカーとして有用であること、また、MIR130 family-BHLHE40/41経路を標的とした分子治療戦略は子宮体癌の進展を抑制する方策として有望であると考える。