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SIRT1和磷酸化SIRT1在结直肠癌中的表达及相关性

The expression and correlation of SIRT1 and Phospho-SIRT1 in colorectal cancer.

作者信息

Zhang Xianzhen, Chen Suiqin, Cheng Meili, Cao Fangli, Cheng Yufeng

机构信息

Department of Radiation Oncology, Qilu Hospital of Shandong University 107#, Wenhua Xi Road, Jinan, China ; Department of Oncology, Liaocheng People's Hospital Liaocheng, China.

Department of Examination Center, Liaocheng People's Hospital Liaocheng, China.

出版信息

Int J Clin Exp Med. 2015 Jan 15;8(1):809-17. eCollection 2015.

Abstract

SIRT1 is the homologue of sir2 in mammals, which is a nicotinamide adenine dinucleotide (NAD(+)) dependent histone deacetylase. SIRT1 is involved in many physiological processes, such as metabolism, senescence, inflammatory response, neuroprotection, and tumorigenesis by acetylating histones and multiple transcription factors. However, the exact role of SIRT1 in tumor is still under controversial. Immunohistochemistry and Western blot were performed to investigate the expressions and subcellular localizations of SIRT1 and Phospho-SIRT1 in colorectal cancer tissues and adjacent normal tissues. The relationship between SIRT1 or Phospho-SIRT1 and clinicopathological characteristics was also analyzed. Real-Time PCR was performed to investigate the transcriptional level of SIRT1 mRNA in colorectal cancer tissues and adjacent normal tissues. SIRT1 and Phospho-SIRT1 were both localized in the nucleus. The expressions of SIRT1 and Phospho-SIRT1 were higher in colorectal cancer tissues than normal tissues. SIRT1 expression in cancer tissues was associated with patient age, TNM stage and mutant P53 loss. Phospho-SIRT1 expression in cancer tissues was associated with Ki67. SIRT1 and Phospho-SIRT1 were highly correlated in cancer tissues and normal tissues. The ratios of Phospho-SIRT1 and SIRT1 expression in cancer tissues were higher than normal tissues. SIRT1 mRNA level was no significant difference in cancer tissues and normal tissues. SIRT1 have a dual character in colorectal cancer, and Phospho-SIRT1 may determine the role of SIRT1 in colorectal cancer formation.

摘要

SIRT1是哺乳动物中sir2的同源物,是一种烟酰胺腺嘌呤二核苷酸(NAD(+))依赖性组蛋白脱乙酰酶。SIRT1通过使组蛋白和多种转录因子乙酰化参与许多生理过程,如代谢、衰老、炎症反应、神经保护和肿瘤发生。然而,SIRT1在肿瘤中的确切作用仍存在争议。采用免疫组织化学和蛋白质印迹法研究SIRT1和磷酸化SIRT1在结直肠癌组织及癌旁正常组织中的表达及亚细胞定位。分析SIRT1或磷酸化SIRT1与临床病理特征之间的关系。采用实时定量聚合酶链反应检测结直肠癌组织及癌旁正常组织中SIRT1 mRNA的转录水平。SIRT1和磷酸化SIRT1均定位于细胞核。结直肠癌组织中SIRT1和磷酸化SIRT1的表达均高于正常组织。癌组织中SIRT1的表达与患者年龄、TNM分期及突变型P53缺失有关。癌组织中磷酸化SIRT1的表达与Ki67有关。癌组织和正常组织中SIRT1与磷酸化SIRT1高度相关。癌组织中磷酸化SIRT1与SIRT1表达的比值高于正常组织。癌组织和正常组织中SIRT1 mRNA水平无显著差异。SIRT1在结直肠癌中具有双重作用,磷酸化SIRT1可能决定SIRT1在结直肠癌形成中的作用。

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