Targeting continuous inflammation in pancreatic cancer microenvironment

针对胰腺癌微环境中的持续炎症

• 批准号: 24790674
• 负责人: HAMADA Shin
• 金额: $ 2.66万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 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/grant/KAKENHI-PROJECT-24790674/
• 关键词: microRNA; アポトーシス; 炎症性シグナル; 浸潤性膵癌; マイクロRNA; 膵癌組織中炎症

We assessed the effect of forced expression of miR-365, which was highly expressed in invasive pancreatic cancer compared with IPMN. miR-365 increased the cell viability of pancreatic cancer cells after the gemcitabine treatment, suggesting the induction of resistance. A comprehensive analysis of gene expression profiles in miR-365 introduced cells identified up-regulation of several NF kappa B target genes. Activation of NF kappa B pathway was confirmed by the increased expression of phosphorylated NF kappa B. On the other hand, miR-365 directly targeted apoptosis-related molecules such as SHC1 and BAX that led to the gemcitabine resistance.

我们评估了 miR-365 强制表达的效果，与 IPMN 相比，miR-365 在侵袭性胰腺癌中高表达。吉西他滨治疗后，miR-365 增加了胰腺癌细胞的细胞活力，表明诱导了耐药性。对引入 miR-365 的细胞中基因表达谱的综合分析发现了几个 NF kappa B 靶基因的上调。磷酸化 NF kappa B 表达增加证实了 NF kappa B 通路的激活。另一方面，miR-365 直接靶向凋亡相关分子，如 SHC1 和 BAX，导致吉西他滨耐药。

项目成果

MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX

• DOI: 10.1016/j.cellsig.2013.11.003
• 发表时间: 2014-02-01
• 期刊: CELLULAR SIGNALLING
• 影响因子: 4.8
• 作者: Hamada, Shin;Masamune, Atsushi;Shimosegawa, Tooru
• 通讯作者: Shimosegawa, Tooru

MiR-365 indirectly regulates drug resistance-related molecule Aryl hydrocarbon receptor nuclear translocator expression in pancreatic ductal adenocarcinoma cells

MiR-365间接调控胰腺导管腺癌细胞耐药相关分子芳烃受体核转位子表达

• 发表时间: 2013
• 作者: Hamada S;Satoh K;Masamune A;Kanno A;Kikuta K;Kume K;Unno J;Hirota M and Shimosegawa T
• 通讯作者: Hirota M and Shimosegawa T

Identification of inflammatory signal-stimulating microRNA in pancreatic duct cell carcinoma

胰腺导管细胞癌中炎症信号刺激 microRNA 的鉴定

• 发表时间: 2013
• 作者: Hamada S;Satoh K;Masamune A;and Shimosegawa T
• 通讯作者: and Shimosegawa T

Identification of invasion-related microRNAs in pancreatic cancer by comprehensive analysis.

综合分析鉴定胰腺癌侵袭相关microRNA。

• 发表时间: 2012
• 作者: Hamada S;Satoh K;Hirota M;Kanno A;Masamune A;Kikuta K;Kume K;Unno J;Shimosegawa T.
• 通讯作者: Shimosegawa T.

MiR-365によるゲムシタビン耐性誘導機構の検討

MiR-365 诱导吉西他滨耐药机制的研究

• 发表时间: 2013
• 作者: Hamada S;et al;林周作,濱田貴之,門脇真;Shinya Suzuki;濱田晋,佐藤賢一,正宗淳,菅野敦,菊田和宏,粂潔,廣田衛久,下瀬川徹
• 通讯作者: 濱田晋,佐藤賢一,正宗淳,菅野敦,菊田和宏,粂潔,廣田衛久,下瀬川徹