Identification of miRNAs involved in the premalignant lesions in gastrointestinal tract and their malignant transformation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17483
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takeuchi Chihiro 東京大学, 医学部附属病院, 届出研究員 (60836055)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: miRNA / 網羅的遺伝子発現解析 / 非乳頭部十二指腸上皮性腫瘍 / Wnt/βcatenin pathway / APC mutation

Outline of Final Research Achievements

We performed comprehensive gene expression analysis of miRNA / mRNA using nonpapillary duodenal epithelial tumors. Gene ontology analysis showed that the expression of the target genes of miR-135b, which was significantly expressed in tumors, was decreased, and that it was associated with the APC gene and Wnt pathway. Indeed, immunostaining using resected specimens showed high expression level of miR-135b and abnormal accumulation of β-catenin. And APC gene mutation was rarely observed in the tumors. The induction of miR-135b expression decreased the expression of APC protein. These results suggested that upregulation of miR-135b may inhibit APC protein expression, leading tumorigenesis through upregulation of Wnt pathway signaling in nonpapillary duodenal epithelial tumors.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

十二指腸上皮性腫瘍の前癌病変と早期癌におけるmiRNAの発現異常とその腫瘍発症機序のメカニズムについて比較検討した報告は少ない。本研究では網羅的遺伝子発現解析と病理学的検討及び基礎的検討を通してmiRNAによる腫瘍発症のメカニズムを明らかにした。消化管において前癌病変・早期癌の初期発症に関与する分子メカニズムを解明する事は、有効な診断法・治療法の確立や化学療法予測を可能にするという点で臨床的意義が大きいと考えられる。