Translational research focusing on the regulation of proteasome by Gankyrin

Gankyrin对蛋白酶体调控的转化研究

• 批准号: 23590998
• 负责人: SAKURAI Toshiharu
• 金额: $ 3.33万
• 依托单位: Kinki 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-23590998/
• 关键词: ガンキリン; 幹細胞; 炎症と発癌; 癌幹細胞; JNK; EMT

Liver-specific p38-alpha ablation was found to enhance ROS accumulation, because it reduced the expression ofHSP25. p38-alpha-deficiency also increased the expression of SOX2, c-Jun and Gankyrin and led to enhanced TAA-induced hepatocarcinogenesis. The up-regulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole. The risk of human HCC recurrence is positively correlated with ROS accumulation in the liver. Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis. In addition, expression of CD133, a cancer stem cell marker, was significantly correlated with Gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal and liver cancer cells.

肝脏特异性p38-α消融被发现增加ROS积累，因为它减少了HSP 25的表达。p38-α缺陷还增加了SOX 2、c-Jun和Gankyrin的表达，并导致TAA诱导的肝癌发生增强。SOX 2和c-Jun的上调通过给予抗氧化剂丁基化羟基茴香醚来防止。人HCC复发的风险与肝脏中ROS积累呈正相关。 肝实质细胞氧化应激增强可能是肝纤维化与肝癌发生的密切关系。此外，肿瘤干细胞标志物CD 133的表达与Gankyrin的表达显著相关。Gankyrin基因敲低可降低结直肠癌和肝癌细胞中血管内皮生长因子（VEGF）和干性因子如Nanog和Oct-4的表达。

项目成果

Risk of Hepatocellular Carcinoma Development in Cases of Hepatitis C Treated by Long-Term, Low-Dose PEG-IFNα-2a

长期低剂量 PEG-IFNα-2a 治疗丙型肝炎患者发生肝细胞癌的风险

• 发表时间: 2012
• 期刊: Dig Dis
• 作者: Hagiwara S;Sakurai T;Takita M;Ueshima K;Minami Y;Inoue T;Yada N;Kitai S;Nagai T;Hayaishi S;Arizumi T;Nishida N;Kudo M
• 通讯作者: Kudo M

Unique association between global DNA hypomethylation and chromosomal alterations in human hepatocellular carcinoma.

• DOI: 10.1371/journal.pone.0072312
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Nishida N;Kudo M;Nishimura T;Arizumi T;Takita M;Kitai S;Yada N;Hagiwara S;Inoue T;Minami Y;Ueshima K;Sakurai T;Yokomichi N;Nagasaka T;Goel A
• 通讯作者: Goel A

慢性膵炎におけるp38MAPK, HSP27の役割

p38MAPK 和 HSP27 在慢性胰腺炎中的作用

• 发表时间: 2013
• 作者: 櫻井俊治;その他
• 通讯作者: その他

ソラフェニブ治療におけるJNK活性の重要性-CD133との関連も含めて-

JNK 活性在索拉非尼治疗中的重要性 - 包括其与 CD133 的关系 -

• 发表时间: 2013
• 作者: 萩原智;櫻井俊治;工藤正俊
• 通讯作者: 工藤正俊

肝細胞癌治療におけるJNK活性の重要性

JNK 活性在肝细胞癌治疗中的重要性

• 发表时间: 2011
• 作者: 萩原智;櫻井俊治;工藤正俊
• 通讯作者: 工藤正俊