Mechanistic analysis of the colorectal cancer progression by MLL mutation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07574
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nagasaki University
• Principal Investigator: Yoneda Mitsuhiro 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80508367)
• Co-Investigator(Kenkyū-buntansha): 伊藤 敬 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90306275)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌

Outline of Final Research Achievements

The proliferation of colon cancer cells with MLL mutant was suppressed by subunits of MLL4 complex knockdown, while the proliferation of colon cancer cells without MLL mutant was not suppressed by the subunits knockdown. As a result, subunits of MLL4 complex facilitated proliferation of colon cancer cells with MLL mutant.
Moreover, we knockdowned MLL4 in colon cancer cells with and without MLL4 mutation to identify MLL4 mutation specific target genes. We purified RNAs from these cells and made libraries for RNA-seq. MLL complex formation was confirmed with Flag, HA, or His tagged recombinant proteins of common MLL complex subunits for in vitro transcription to clarify the mechanism.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

本研究は、ヒストンH3リシン4番目(H3K4)メチル化酵素Mixed Lineage Leukemia (MLL)の遺伝子変異がエピゲノム変化をもたらし、細胞を癌化させる分子メカニズムを解明することが最終目標である。MLL遺伝子変異を有する（変異型MLL）大腸癌細胞においてMLLの標的癌遺伝子または癌抑制遺伝子を網羅的に同定し、癌化経路特定の足がかりとする。
本研究は、MLL遺伝子変異を有する固形癌に対する早期診断・予後診断や、より有効な分子標的療法の発見につながる礎となる可能性を秘めている。