Regulatory mechanism of intestinal tumorigenesis by TMEPAI

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: NAKANO Naoko 昭和薬科大学, 薬学部, 講師 (50733218)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: TMEPAI / ApcΔ716/+ / ノックアウトマウス / 腸オルガノイド

Outline of Final Research Achievements

We tried RNA sequencing using total RNAs from intestinal epithelial cells between ApcΔ716/+ and TmepaiKO/ApcΔ716/+ mice. We could observe about 30 genes whose expressions were different between ApcΔ716/+ and TmepaiKO/ApcΔ716/+ mice. At present, We are trying to examine if these genes are involved in loss of tumorigenicity in intestines from TmepaiKO/ApcΔ716/+ mice. In addition, We established small intestinal organoids from ApcΔ716/+ and TMEPAI KO/ApcΔ716/+ mice and examined their proliferative ability, and found that the expansion rate of organoids from TMEPAI KO/ApcΔ716/+ mice was suppressed. Currently, We are establishing organoids with high expression of candidate genes in each organoid and examining the effect on tumorigenic potential.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

TMEPAI KO/ApcΔ716/+マウスにおいて、ApcΔ716/+マウスに比較して消化管腺腫形成が著しく抑制される結果が得られている。APC遺伝子は家族性大腸腺腫症 (FAP) の原因遺伝子として単離され、また、APC遺伝子の変異は大腸がんにおいても高頻度に検出されている。さらに、TMEPAIは大腸がんや様々ながんで発現が上昇していることも報告されていることから、TMEPAI遺伝子欠損による消化管腺腫抑制メカニズムを明らかにすることで、新規の消化管腫瘍治療法や抗がん剤開発につながると考えている。