Identification and analysis of functional RNAs regulated by p53 family members in gastrointestinal tumorigenesis

p53家族成员在胃肠道肿瘤发生中调控的功能RNA的鉴定和分析

• 批准号: 23590920
• 负责人: SASAKI Yasushi
• 金额: $ 3.24万
• 依托单位: Sapporo Medical 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-23590920/
• 关键词: p53; p73; p63; 機能性RNA; miRNA; 消化器癌; バイオマーカー

The miR-200 family includes two clusters: miR-200b-200a-429 located on chromosome 1; and miR-200c-141 located on chromosome 12. We identified response elements located around both clusters that are responsive to p53 family. Here, in silico miRNA target prediction identified the v-crk sarcoma virus CT10 oncogene homolog-like (CRKL) as a potential miR-200b/200c/429 target. MiR-200b/200c/429 inhibits the expression of CRKL by directly targeting its 3'-UTR region. Importantly, CRKL expression was decreased in cancer cells with introduction of wild-type p53 and TAp63. Oncomine database shows that CRKL levels are significantly overexpressed in multiple cancer types compared with the corresponding normal tissues. We also found that CRKL was overexpressed in primary breast cancer tissues harboring mutant p53 genes. Our results indicate that a p53-inducible miRNA, 200b/200c/429 is a negative regulator of the CRKL oncoprotein and suggest a new p53-miR-200-CRKL pathway in carcinogenesis.

miR-200家族包括两个簇：位于1号染色体上的miR-200b-200a-429；和位于12号染色体上的miR-200c-141。我们确定了位于两个簇周围的对p53家族有反应的反应元件。本研究中，miRNA靶标预测将v-crk肉瘤病毒CT10癌基因同源样物（CRKL）鉴定为潜在的miR-200b/200c/429靶标。MiR-200b/200c/429通过直接靶向CRKL的3'-UTR区域抑制CRKL的表达。重要的是，引入野生型p53和TAp63后，癌细胞中CRKL的表达降低。Oncomine数据库显示，与相应的正常组织相比，CRKL水平在多种癌症类型中显著过表达。我们还发现CRKL在携带p53突变基因的原发性乳腺癌组织中过表达。我们的研究结果表明，p53诱导的miRNA 200b/200c/429是CRKL癌蛋白的负调节因子，并提示了p53-miR-200-CRKL在癌变过程中的新途径。

项目成果

ゲノム網羅的shRNAライブラリースクリーニングによるp53誘導アポトーシス阻害遺伝子の同定

通过全基因组shRNA文库筛选鉴定p53诱导的凋亡抑制基因

• 发表时间: 2012
• 作者: Idogawa M;Sasaki Y;Shinomura Y;Imai K;Tokino T;佐々木泰史，井戸川雅史，時野隆至;井戸川雅史，大箸智子，佐々木泰史，篠村恭久，今井浩三，時野隆至;田村みゆき，佐々木泰史，井戸川雅史，時野隆至;大箸智子，井戸川雅史，佐々木泰史，時野隆至
• 通讯作者: 大箸智子，井戸川雅史，佐々木泰史，時野隆至

p53ファミリーの新規標的遺伝子FOXF1の同定と機能解析

p53家族新靶基因FOXF1的鉴定及功能分析

• 发表时间: 2011
• 作者: 田村みゆき，佐々木泰史;横田育子;鹿島理沙;井戸川雅史;時野隆至
• 通讯作者: 時野隆至

p53 regulates negatively the expression of the nuclear export protein XPO1, establishing a positive feedback loop

p53 负向调节核输出蛋白 XPO1 的表达，建立正反馈环

• 发表时间: 2014
• 作者: Sasaki Y;Tamura M;Kobayashi T;Idogawa M;Suzuki H;Shinomura Y;Tokino T
• 通讯作者: Tokino T

Apoptosis induction in p53-mutated cancer cells by shRNAs based on the screening of genome-wide shRNA library

基于全基因组shRNA文库筛选的shRNA诱导p53突变癌细胞凋亡

• 发表时间: 2013
• 作者: Ohashi T;Idogawa M;Sugisaka J;Tamura M;Yokota I;Sasaki Y;Tokino T
• 通讯作者: Tokino T

Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat

• DOI: 10.1007/s00535-010-0320-7
• 发表时间: 2011-02
• 期刊: Journal of Gastroenterology
• 影响因子: 6.3
• 作者: Hiroki Tanaka;Y. Arimura;Takashi Yabana;A. Goto;M. Hosokawa;Kanna Nagaishi;K. Yamashita;Hiroyuki Yamamoto;Y. Sasaki;M. Fujimiya;K. Imai;Y. Shinomura