Identification of microRNA which regulates peritoneal dissemination of ovarian cancer

调节卵巢癌腹膜播散的 microRNA 的鉴定

• 批准号: 21791555
• 负责人: SAWADA Kenjiro
• 金额: $ 2.5万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791555/
• 关键词: マイクロRNA; 腹膜播種; 卵巣癌; インテグリン; 播種; インテグリンa5

Ovarian cancer is a highly metastatic characterized by widespread peritoneal dissemination and ascites, and is the leading cause of death from gynecological malignancy. We have previously identified integrinα5 as a new target in ovarian cancer treatment by inhibiting peritoneal dissemination. Our aim is to identify new microRNA which regulates the expression of integrinα5 and analyze the therapeutic potential of targeting of its microRNA. Based on the microRNA algorism search, we identified hsa-mir-92a as a candidate. Hsa-mir-92a is little expressed in ovarian cancer cells which express high level of integrinα5, whereas hsa-mir-92a is highly expressed in RMUG-S cells which do not express integrinα5. Transfection of precursor mir-92a reduced integrinα5 expression in ovarian cancer cells, accompanied by the inhibition of cell adhesion and invasion. Those results suggested targeting hsa-mir-92a could be a promising therapy for a subset of ovarian cancer patients by inhibiting integrin α5 expression.

卵巢癌是一种以广泛的腹膜播散和腹水为特征的高度转移性肿瘤，是妇科恶性肿瘤死亡的主要原因。我们之前已经发现整合素α5通过抑制腹膜播散作为卵巢癌治疗的新靶点。我们的目的是鉴定新的调控整合素α5表达的microRNA，并分析其靶向microRNA的治疗潜力。基于microRNA算法搜索，我们确定了hsa-mir-92a作为候选基因。Hsa-mir-92a在高水平表达整合素α5的卵巢癌细胞中表达少，而在不表达整合素α5的RMUG-S细胞中表达高。转染前体mir-92a可降低整合素α5在卵巢癌细胞中的表达，同时抑制细胞粘附和侵袭。这些结果表明，通过抑制整合素α5的表达，靶向hsa-mir-92a可能是一种有希望的治疗卵巢癌患者亚群的方法。

项目成果

CD95 promotes tumour growth.

• DOI: 10.1038/nature09075
• 发表时间: 2010-05-27
• 期刊: Nature
• 影响因子: 64.8

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.

Up-regulation of alpha5-integrin by E-cadherin loss in hypoxia and its key role in the migration of extravillous trophoblast cells during early implantation.

缺氧时 E-钙粘蛋白损失上调 α5-整合素及其在早期着床过程中绒毛外滋养层细胞迁移中的关键作用。

• 发表时间: 2009
• 期刊: Endocrinology 150(9)
• 作者: Arimoto-Ishida E;Sakata M;Sawada K;Nakayama M;Nishimoto F;Mabuchi S;Takeda T;Yamamoto T;Isobe A;Okamoto Y;Lengyel E;Suehara N;Morishige K;Kimura T.
• 通讯作者: Kimura T.