IR@PKUHSC  > 北京大学基础医学院
学科主题临床医学
Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis
Zhang, Qian1,2; Zhang, Lian1,2; Li, Lili3,4; Wang, Zhaohui3; Ying, Jianming5,6; Fan, Yu1,2; Xu, Ben1,2; Wang, Lu1,2; Liu, Qianling1,2; Chen, Guangfu7; Tao, Qian3,4; Jin, Jie1,2
关键词Irf8 Methylation Epigenetic Tumor Suppressor Renal Carcinoma
刊名CANCER LETTERS
2014-11-28
DOI10.1016/j.canlet.2014.07.040
354期:2页:227-234
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]DNA METHYLATION ; TRANSCRIPTION FACTORS ; MYELOID CELLS ; PROTEIN ABUNDANCE ; CLEAR-CELL ; EXPRESSION ; GENE ; APOPTOSIS ; ACTIVATION ; MULTIPLE
英文摘要

Interferon regulatory factor 8 (IRF8), as a central element of IFN-gamma-signaling, plays a critical role in tumor suppression. However, its expression and underlying molecular mechanism remain elusive in renal cell carcinoma (RCC). Here, we examined IRF8 expression and methylation in RCC cell lines and primary tumors, and further assessed its tumor suppressive functions. We found that IRF8 was widely expressed in human normal tissues including kidney, but frequently downregulated by promoter methylation in RCC cell lines. IRF8 methylation was detected in 25% of primary tumors, but not in adjacent non-malignant renal tissues, and associated with higher tumor nuclear grade of RCC. Ectopic expression of IRF8 inhibited colony formation and migration abilities of RCC cells, through inducing cell cycle G2/M arrest and apoptosis. IFN-gamma could induce IRF8 expression in RCC cells, together with increased cleaved-PARR We further found that IRF8 inhibited expression of oncogenes YAP1 and Survivin, as well as upregulated expression of tumor suppressor genes CASP1, p21 and PTEN. Collectively, our data demonstrate that IRF8 as a functional tumor suppressor is frequently methylated in RCC, and IRF8-mediated interferon signaling is involved in RCC pathogenesis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

语种英语
WOS记录号WOS:000344127600003
项目编号81272290 ; 81171971 ; 81372898 ; 81101492 ; JC201005270328A
资助机构National Natural Science Foundation ; Scientific Fund for Distinguished Young Scholars of Shenzhen
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55055
专题北京大学基础医学院
北京大学第一临床医学院_泌尿外科
作者单位1.Peking Univ, Hosp 1, Dept Urol, Beijing 100034, Peoples R China
2.CUHK Shenzhen Res Inst, Shatin, Hong Kong, Peoples R China
3.Natl Res Ctr Genitourinary Oncol, Inst Urol, Beijing 100034, Peoples R China
4.Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, Dept Clin Oncol, Canc Epigenet Lab,State Key Lab Oncol South China, Shatin, Hong Kong, Peoples R China
5.Chinese Acad Med Sci, Peking Union Med Coll, Inst Canc, Dept Pathol, Beijing 100021, Peoples R China
6.Chinese Acad Med Sci, Peking Union Med Coll, Canc Hosp, Beijing 100021, Peoples R China
7.PIA Gen Hosp, Med Sch Chinese PLA, Dept Urol, Beijing 100853, Peoples R China
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GB/T 7714
Zhang, Qian,Zhang, Lian,Li, Lili,et al. Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis[J]. CANCER LETTERS,2014,354(2):227-234.
APA Zhang, Qian.,Zhang, Lian.,Li, Lili.,Wang, Zhaohui.,Ying, Jianming.,...&Jin, Jie.(2014).Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis.CANCER LETTERS,354(2),227-234.
MLA Zhang, Qian,et al."Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis".CANCER LETTERS 354.2(2014):227-234.
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