molecular diagnosis and target therapy for cervical cancer by microRNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11300
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Fujita Health University
• Principal Investigator: FUJII TAKUMA 藤田医科大学, 医学部, 教授 (10218969)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 子宮頸がん / マイクロRNA / 子宮頸部異形成 / 検診 / 分子標的治療 / 分子診断 / 細胞増殖 / マイクロアレイ

Outline of Final Research Achievements

MicroRNAs (miRNAs) play important roles in the regulation of gene expression during cervical carcinogenesis. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) in cervical mucus were significantly upregulated in precancer and cancer compared with normal, and their expression levels correlated with the disease severity. miRNAs in cervical mucus are promising biomarkers for cervical cancer and its precursor lesions.
Next, we investigated the effects of enforced miR-126-3p expression in the cervical cancer cell line, HeLa. In miR-126-3p-transfected cells, p85b, p110a, p-PDK1, p- AKT, p-GSK3b, CyclinD1, MRCKa, ROCK1, and p- PLCg1 were downregulated, Bad and Bax were upregulated, whereas Bcl-xL expression was downregulated, resulting in increased caspase3/7 activity and apoptosis. High levels of miR-126-3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR-126-3p could represent a new approach for treating patients with cervical cancer.

Free Research Field

婦人科

Academic Significance and Societal Importance of the Research Achievements

子宮頸がんスクリーニング法は細胞診で行われているが、欧米諸国の臨床試験の結果では感度７割と高くない。頸管粘液中のmiRNAには頸部前がん病変から過剰発現しているものがあり、それを計測することで早期補助診断が可能であることが分かった。このmiRNAは細胞内に強制的に発現すると癌細胞の増殖を抑制することがわかり、新たな子宮頸がんに対する分子標的治療開発の可能性も示唆された。