Drug repositioning strategy of head and neck squamous cell carcinoma after treatment failure based on microRNA analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Chiba University
• Principal Investigator: Kikkawa Naoko 千葉大学, 大学院医学研究院, 特任講師 (50400924)
• Co-Investigator(Kenkyū-buntansha): 関 直彦 千葉大学, 大学院医学研究院, 准教授 (50345013) ; 花澤 豊行 千葉大学, 大学院医学研究院, 教授 (90272327)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 頭頸部扁平上皮癌 / マイクロRNA / miR-199

Outline of Final Research Achievements

MicroRNA expression profile was created using clinical specimens of Head and neck squamous cell carcinoma(HNSCC） treatment failure. Analysis of the profile revealed that member of miR-199-family were downregulated in HNSCC tissues. Ectopic expression assays showed that these miRNAs significantly inhibited cancer cell aggressiveness. Our in silico analysis and luciferase reporter assay identified paxillin (PXN) as a direct target of miR-199-family in HNSCC cells. Overexpression of PXN was detected in HNSCC clinical specimens by immunostaining. Analysis of the cancer genome atlas (TCGA) database showed that expression of PXN significantly predicted a worse prognosis (5-year overall survival rate; p = 0.0283). Furthermore, functional assays in HNSCC cells showed that knockdown of PXN expression attenuated cancer cell migration and invasion, suggesting that aberrant expression of PXN contributed to HNSCC cell aggressiveness.

Free Research Field

耳鼻咽喉・頭頸部腫瘍学

Academic Significance and Societal Importance of the Research Achievements

頭頸部扁平上皮癌(HNSCC)の初回治療後の、再発症例・遠隔転移症例の予後は極めて不良であり、平均生存期間は、数ヶ月とされている。HNSCC細胞が治療過程に獲得した再発・遠隔転移(治療抵抗性)に関わる分子経路の解明や新規治療法の開発が急務である。今回、治療抵抗性HNSCCの臨床検体におけるマイクロRNA発現プロファイルを起点とした解析により、癌抑制型マイクロRNAと標的癌促進型遺伝子を含む、新規分子経路を明らかにすることができた。新規治療法の開発に向けて有用な情報を得られたと考えられる。