Analysis of microRNA function on heart and smooth muscles and itsanti-tumor effect using genetically modified mice

转基因小鼠分析microRNA对心脏和平滑肌的功能及其抗肿瘤作用

• 批准号: 22590369
• 负责人: IWAMOTO Takashi
• 金额: $ 2.91万
• 依托单位: Chubu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590369/
• 关键词: マイクロ RNA; トランスジェニックマウス; 癌; 拡張型心筋症; マイクロＲＮＡ; アンジオテンシン変換酵素; マイクロRNA; 大腸癌; c-Myc; p68/p72; 心不全; 心筋細胞

Although accumulating evidence has shown that microRNAs are involved in many human diseases, the molecular mechanisms are still unknown. In this project, we reveal that strong expression of certain microRNAs suppresses the intestine tumor development in the model mice of familial adenomatous polyposis and that cooperation of miRNAs plays pivotal roles in inhibiting protooncogene expression. We further show that key components for biogenesis of a subset of tumor suppressor microRNAs are downregulated in the transgenic tumors. These data indicate the complicated feedback inhibition between micoRNAs and molecules for their biogenesis. This project also demonstrates that their strong expression in mouse heart inducescardiomyopathy, partially clarifying its molecular mechanisms.

尽管越来越多的证据表明microRNA与许多人类疾病有关，但其分子机制仍不清楚。在这个项目中，我们揭示了某些 microRNA 的强表达抑制了家族性腺瘤性息肉病模型小鼠的肠道肿瘤发展，并且 miRNA 的合作在抑制原癌基因表达中发挥着关键作用。我们进一步表明，在转基因肿瘤中，肿瘤抑制 microRNA 子集的生物发生的关键成分被下调。这些数据表明 microRNA 和分子之间对其生物发生存在复杂的反馈抑制。该项目还证明它们在小鼠心脏中的强表达会诱发心肌病，部分阐明了其分子机制。

项目成果

β-Catenin signaling regulates the timing of cell differentiation in mouse retinal progenitor cells

β-连环蛋白信号传导调节小鼠视网膜祖细胞的细胞分化时间

• DOI: 10.1016/j.mcn.2011.02.010
• 发表时间: 2011
• 期刊: Mol Cell Neurosci
• 影响因子: 3.5
• 作者: Ouchi Y;Baba Y;Koso H;Taketo MM;Iwamoto T;Aburatani H;Watanabe S
• 通讯作者: Watanabe S

家族性大腸腺腫症モデルマウスにおけるmiR-143 の発がん抑制機能解析

家族性腺瘤性息肉病模型小鼠miR-143致癌抑制功能分析

• 发表时间: 2010
• 作者: Shimizu Y.;Hasegawa H.;Ouchi Y.,Iwamoto T.
• 通讯作者: Ouchi Y.,Iwamoto T.

Mimosine-Induced Apoptosis in C6 Glioma Cells Requires the Release of Mitochondria-Derived Reactive Oxygen Species and p38, JNK Activation

• DOI: 10.1007/s11064-011-0628-6
• 发表时间: 2011-10
• 期刊: Neurochemical Research
• 影响因子: 4.4
• 作者: Shanlou Qiao;K. Murakami;Qinghong Zhao;Bao Wang;H. Seo;H. Yamashita;Xiaotao Li;T. Iwamoto;M. Ichihara;M. Yoshino

Deficiency of DGCR8 gene, a potential gene for 22q11 deletion syndrome, decreases adult neurogenesis in the mouse hippocampal dentate gyrus

DGCR8 基因（22q11 缺失综合征的潜在基因）的缺陷会减少小鼠海马齿状回的成体神经发生

• 发表时间: 2011
• 作者: Takahiro Yamazaki;Yoshinori Ikarashi et al.;伊波 英克;Haorile Chagan-Yasutan;久保秀司;大内靖夫
• 通讯作者: 大内靖夫

The heterochrinic gene Lin-28 regulates cell proliferation and neural expansion during early development in zebrafish

异质基因 Lin-28 调节斑马鱼早期发育过程中的细胞增殖和神经扩张

• 发表时间: 2011
• 作者: Aida K;Udagawa T;Narumi K;Suzuki K;Goto N;Ikarashi Y;Ohnami S;Yoshida T;Aoki K;平島光臣;仁木敏朗;Kubo S;山本純矢
• 通讯作者: 山本純矢