Mechanism for the selection of anti-cancer networks by tumor-suppressive miRNAs

肿瘤抑制 miRNA 选择抗癌网络的机制

• 批准号: 23300359
• 负责人: TSUCHIYA Naoto
• 金额: $ 5.99万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-11-18 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23300359/
• 关键词: ｍｉＲＮＡ; マイクロRNA; がん抑制因子; 発がん; 癌; 細胞周期; 発がんバリアー; 腫瘍学; miRNA

By detailed analysis of miR-101 and miR-22, we successfully found novel intra-cellular networks, which are deeply involved in the regulation of cancer cell proliferation. miR-101 was defined as a novel regulator for G2 checkpoint of cell cycle through the repression of several microtubule regulators, and resulted in its function as a inducer of p53-dependent apoptosis. We also confirmed that expression of miR-101 is frequently down-regulated in human cancers.We identified NEK9 as a crucial regulator for cell cycle progression in p53-inactivated cancer cells through the target screening of miR-22. Knockdown of NEK9 was caused to repress cell proliferation only in p53 mutant and deficient cells both in vitro and in vivo. NEK9 KD was indicated to induce prolonged inhibition of G1 to S progression of cell cycle leading to express senescence-like features of cancer cells. Our findings might provide a novel strategy for cancer therapy targeting mutant p53.

通过对miR-101和miR-22的详细分析，我们成功地发现了新的细胞内网络，这些网络深入参与了癌细胞增殖的调控。miR-101是一种新型的细胞周期G2检查点调控因子，通过抑制多种微管调控因子，诱导p53依赖的细胞凋亡。我们还证实了miR-101在人类癌症中的表达经常下调。我们通过miR-22的靶向筛选，确定NEK 9是p53失活的癌细胞中细胞周期进程的关键调节因子。在体外和体内，NEK 9的敲除仅在p53突变体和缺陷细胞中引起细胞增殖抑制。NEK 9 KD被指示诱导细胞周期的G1至S进展的延长抑制，导致表达癌细胞的衰老样特征。我们的研究结果可能为靶向突变型p53的癌症治疗提供一种新的策略。

项目成果

Comprehensive analysis of plasma exosomal miRNAs in patients with cancer

癌症患者血浆外泌体miRNA的综合分析

• 发表时间: 2013
• 作者: Ogata-Kawata H;Izumiya M;Yamada Y;Okusaka T;Kohno T;Yokota J;Tsuchiya N
• 通讯作者: Tsuchiya N

MiR-101 as a molecular switch for sequential activation of p53-dependent G1 and G2 checkpoints in response to ribosomal stress

MiR-101 作为分子开关，用于响应核糖体应激而顺序激活 p53 依赖性 G1 和 G2 检查点

• 发表时间: 2013
• 作者: Tsuchiya N;Fujiwara Y;Nakagama H;Kohno T;Yokota J
• 通讯作者: Yokota J

miRNA profiles in exosomes derived from lung cancer cells

肺癌细胞外泌体中的 miRNA 谱

• 发表时间: 2012
• 作者: Kobayashi T;Ogata-Kawata H;Murakami Y;Yokota J;Tsuchiya N
• 通讯作者: Tsuchiya N

がん抑制的miRNAs－効率な単離法から機能解析まで－

肿瘤抑制 miRNA - 从有效的分离方法到功能分析 -

• 发表时间: 2012
• 期刊: 遺伝子医学MOOK
• 作者: 土屋直人

新たながん克服医療の構築-マイクロ RNA 変動に起因するがんの病態把握と革新的な診断法・予防法及び核酸医薬の開発-

构建抗癌新药 - 了解microRNA波动引起的癌症病理学，开发创新诊断和预防方法以及核酸药物 -

• 发表时间: 2013
• 作者: 藤原 稔史;福士 純一;松本 嘉寛;渡 公佑;小野 眞弓;桑野 信彦;飯田 圭一郎;岡田 悠子;岩本 幸英;土屋直人
• 通讯作者: 土屋直人