Crosstalk between CagA and inflammation in H. pylori-related gastric carcinogenesis.

CagA 与幽门螺杆菌相关胃癌发生中炎症之间的串扰。

• 批准号: 24659365
• 负责人: TSUJII Masahiko
• 金额: $ 2.25万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659365/
• 关键词: 胃癌; ヘリコバクターピロリ; CagA; 腸上皮化生; 胃炎; let-7; 炎症

In in vitro experiments, CagA significantly attenuated let-7 expression leading to Ras pathway activation. CagA enhanced c-myc, DNA methyltransferase 3B (DNMT3B) and Enhancer of Zeste homologue 2 (EZH2) expression and attenuated miR-26a and miR-101 expression, which resulted in the attenuation of let-7 expression by histone and DNA methylation. Experiments performed in CagA transgenic mice revealed that c-myc, EZH2 and DNMT3B expression were enhanced and let-7 expression was attenuated to induce Ras oncoprotein expression in the stomach, with no associated inflammation. It is concluded that H pylori CagA induces aberrant epigenetic silencing of let-7 expression, leading to Ras upregulation.

在体外实验中，CAGA显着减弱了Let-7的表达，导致RAS途径激活。 CAGA增强了C-MYC，DNA甲基转移酶3B（DNMT3B）和ZESTE同源物2（EZH2）表达的增强子，并减弱miR-26a和miR-101表达，从而导致组蛋白和DNA甲基化衰减LET-7表达。在CAGA转基因小鼠中进行的实验表明，C-MYC，EZH2和DNMT3B表达得到增强，并减弱LET-7表达以诱导胃中的Ras癌蛋白表达，而没有相关的炎症。得出的结论是，幽门螺杆菌CAGA诱导Let-7表达的异常表观遗传沉默，从而导致RAS上调。

项目成果

Role of DNA methylation on epithelial mesenchymal transition (EMT)-like phenotype of colon cancer cells

DNA甲基化对结肠癌细胞上皮间质转化（EMT）样表型的作用

• 发表时间: 2012
• 作者: Kondo J;Nishida T;Watabe K;Tsujii M;Takehara T.
• 通讯作者: Takehara T.

Biomarkers in the diagnosis and therapy of inflammatory bowel diseases

炎症性肠病诊断和治疗中的生物标志物

• 发表时间: 2012
• 期刊: 日本臨床
• 作者: Iijima;H. Shinzaki;S. Tsujii;M. et al.
• 通讯作者: M. et al.

Long-term outcomes of ESD for patients with early gastric cancer and liver cirrhosis : a multicenter study by Osaka University ESD Study Group

ESD 对早期胃癌和肝硬化患者的长期结果：大阪大学 ESD 研究小组的一项多中心研究

• 发表时间: 2012
• 作者: Kato M;Tsujii M;Takehara T.
• 通讯作者: Takehara T.

Esophageal pyogenic granuloma developed after short-term fol low-up.

短期随访后出现食管化脓性肉芽肿。

• DOI: 10.1111/j.1442-2050.2012.01351.x
• 发表时间: 2013
• 期刊: Dis Esophagus
• 影响因子: 2.6
• 作者: Saito Y;Nishida T;Kato M;et al.
• 通讯作者: et al.

Epste in-Barr virus-associated early gastric cancer presenting as an elevated lesion.

Epste in-Barr 病毒相关的早期胃癌表现为升高的病变。

• DOI: 10.1055/s-0032-1309353
• 发表时间: 2012
• 期刊: Endoscopy
• 影响因子: 9.3
• 作者: Yamamoto S;Nishida T;Tsujii M;et al.
• 通讯作者: et al.