Identification of micro RNAs which affected by tumor microenvironments of ovarian cancer and analysis of a potential as a therapeutic target

受卵巢癌肿瘤微环境影响的微小RNA的鉴定及其作为治疗靶点的潜力分析

• 批准号: 23592447
• 负责人: SAWADA Kenjiro
• 金额: $ 3.33万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592447/
• 关键词: 卵巣癌; 腹膜播種; 腹膜中皮細胞; マイクロRNA; 骨髄由来細胞

During the dissemination of ovarian cancer cells, cells are floating in the peritoneal cavity without vascular supply and exposed in hypoxic conditions. We suggest that hypoxic stimuli affect ovarian cancer cell behavior. In this study, we screened miRNAs which expression were altered under hypoxic condition. miRNA PCR arrays revealed that the expression of miR-199a-3p decreased under hypoxic conditions. In silico analyses led us to consider MET is one of the target genes of miR-199a-3p. miR-199a-3p expression was inversely correlated with c-Met expression in ovarian cancer cells. Transfection of precursor miR-199a-3p into ovarian cancer cells reduced c-Met expression followed by the inhibition of the proliferation, adhesion and invasion. In an ovarian cancer xenograft model, the enforced expression of miR-199a-3p in SKOV3 cells significantly suppressed peritoneal dissemination. Thus we suggested that miR-199a-3p is a potential target for treating ovarian cancer dissemination.

在卵巢癌细胞的传播过程中，细胞漂浮在没有血管供应的腹膜腔中，并暴露在缺氧条件下。我们认为，低氧刺激影响卵巢癌细胞的行为。在本研究中，我们筛选了在缺氧条件下表达改变的miRNAs。miRNA PCR芯片显示，低氧条件下miR-199 a-3 p表达降低。计算机模拟分析使我们认为MET是miR-199 a-3 p的靶基因之一。卵巢癌细胞中miR-199 a-3 p表达与c-Met表达呈负相关。转染前体miR-199 a-3 p可降低卵巢癌细胞c-Met的表达，抑制其增殖、粘附和侵袭。在卵巢癌异种移植模型中，SKOV 3细胞中miR-199 a-3 p的强制表达显著抑制了腹膜播散。因此，我们认为miR-199 a-3 p是治疗卵巢癌播散的潜在靶点。

项目成果

Identification of microRNA which regulates peritoneal dissemination of ovarian cancer

调节卵巢癌腹膜播散的 microRNA 的鉴定

• 发表时间: 2011
• 作者: Ohyagi;C.
• 通讯作者: C.

腹膜播種を制御するmicroRNAの同定とその作用機序の解明

控制腹膜传播的 microRNA 的鉴定并阐明其作用机制

• 发表时间: 2012
• 期刊: 産科と婦人科
• 作者: Maeda D;Shibahara J;Sakuma T;Isobe M;Teshima S;Mori M;Oda K et al;Yamada Y,Miyamoto T,Asaka R,Ishikawa k,Kobara H,Suzuki A,Shiozawa;端晶彦他;澤田健二郎
• 通讯作者: 澤田健二郎

Ligand-independent activation of c-Met by fibronectin and alpha(5)beta(1)-integrin regulates ovarian cancer invasion and metastasis

纤连蛋白和α(5)β(1)-整合素对c-Met的配体独立激活调节卵巢癌的侵袭和转移

• 发表时间: 2011
• 期刊: Oncogene
• 影响因子: 8
• 作者: Mitra;A. K.;K. Sawada;et al.
• 通讯作者: et al.

Estradiol and raloxifene induce the proliferation of osteoblasts through G-protein-coupled receptor GPR30

雌二醇和雷洛昔芬通过 G 蛋白偶联受体 GPR30 诱导成骨细胞增殖

• 发表时间: 2013
• 期刊: J Endocrinol Invest
• 影响因子: 5.4
• 作者: Noda-Seino;H. Sawada;K. Hayakawa;J. Ohyagi-Hara;C. Mabuchi;S. Takahashi;K. Nishio;Y. Sakata;M. Kurachi;H. Kimura;T.
• 通讯作者: T.

The Activity of Trabectedin As a Single Agent or in Combination with Everolimus for Clear Cell Carcinoma of the Ovary

• DOI: 10.1158/1078-0432.ccr-10-2987
• 发表时间: 2011-07-01
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Mabuchi, Seiji;Hisamatsu, Takeshi;Kimura, Tadashi
• 通讯作者: Kimura, Tadashi