Functional analysis about novel gene which was extracted from gene analyses using gene expression data of epithelial-mesenchymal transition (EMT) genes and drug sensitivities of antitumor agents

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Yamade Mihoko (山出) 浜松医科大学, 医学部, 助教 (10464124)
• Co-Investigator(Kenkyū-buntansha): 古田 隆久 浜松医科大学, 医学部附属病院, 准教授 (10303546)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 上皮間葉転換 / 癌の転移浸潤 / 大腸癌 / 遺伝子発現 / 薬剤感受性

Outline of Final Research Achievements

Epithelial-Mesenchymal transition (EMT) is one of the important mechanisms in cancer invasion and metastasis. Expression levels of EMT genes are also expected to predict cancer prognosis and drug sensitivity. In this study, we investigated a novel gene related to EMT.
We analyzed expression databases of cancer cell lines and cancer tissues and identified LIX1-like (LIX1L) gene, which had strong correlation with well-known EMT genes. We knocked out LIX1L expression of colon cancer cell lines with CRISPR/Cas9 system and investigated their characteristics. We did not find out significant differences between LIX1L-wild type and -knock out cell lines in expression levels of EMT genes, motility and invasion ability with colon cancer cell lines. We continued verification experiments about drug sensitivity to anticancer agents. We are also looking into novel correlation between LIX1L and another genes by microarray.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

切除不能進行癌の薬物治療は昨今新たな薬剤の開発もされている分野であるが、現場で化学療法の治療効果や有害事象を事前に予測することは依然困難である。これらを予測し最善の治療選択につなげるバイオマーカーの開発が必要とされている。
本研究では癌の転移浸潤機構に関わる上皮間葉転換に着目し、LIX1L遺伝子が強い関連性を示すことを見出した。転移浸潤能そのものに現時点で明らかな差異を認めないが、薬剤感受性に関し実験を継続中である。当該遺伝子発現レベルで抗腫瘍薬の効果に差を認めた場合、癌組織のLIX1L発現を治療前に測定することで、より効果的な化学療法レジメンの効果予測が可能になると期待される。