Analysis of comprehensive gene regulation systems in oral cancer stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K11064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hokkaido University
• Principal Investigator: YASUDA MOTOAKI 北海道大学, 歯学研究院, 准教授 (90239765)
• Co-Investigator(Kenkyū-buntansha): 東野 史裕 北海道大学, 歯学研究院, 准教授 (50301891)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 口腔がん / 非翻訳領域 / Hu タンパク質

Outline of Final Research Achievements

HuR has been shown to stabilize ARE mRNA. Clinicopathological reports have demonstrated that the higher expression of HuR is one of the important prognostic factors of malignant tumor cases. In the present study, we found the novel functions of HuB, a neuron specific ELAV member, in oral squamous-cell carcinoma cell lines. The lower differentiated quamous-cell carcinoma cell (SAS) expressed a higher amount of HuB mRNA whereas the highly differentiated squamous-cell carcinoma cell (HSC2) expressed only a small amount of HuB mRNA. On the other hand,HuB transfected HSC2 (HSC2-HuB) showed an obvious nuclear export of HuR in the HuB dependent manner. The higher expressions of ARE mRNAs were observed in HSC2-HuB cells which expressed exogenous HuB. We also demonstrated that HSC2-HuB showed a modest keratinization morphology compared with parental HSC2 cells.

Free Research Field

口腔微生物学

Academic Significance and Societal Importance of the Research Achievements

ELAVL1/HuRはARE mRNAを特異的に安定化させ、その細胞質局在が悪性腫瘍症例の予後と相関することが報告されている。今回、悪性型がん細胞株では神経特異的なELAVL2/HuBが発現しており、HuBとHuRが複合体を形成して核外移行することによりがん幹細胞性が維持されている可能性が示された。このメカニズムは口腔扁平上皮がんのがん幹細胞制御の新たな標的になりうると考えられる。