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学科主题临床医学
Methylation-associated inactivation of LATS1 and its effect on demethylation or overexpression on YAP and cell biological function in human renal cell carcinoma
Chen, Ke-Hong1; He, Jiang2; Wang, De-Lin1; Cao, Jian-Jia1; Li, Mei-Cai1; Zhao, Xiu-Min1; Shen, Xia1; Li, Wen-Bin1; Liu, Wu-Jiang3
关键词Lats1 Renal Cell Carcinoma Methylation Demethylation Hippo Yap
刊名INTERNATIONAL JOURNAL OF ONCOLOGY
2014-12-01
DOI10.3892/ijo.2014.2687
45期:6页:2511-2521
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者National Natural Science Foundation of P.R. China ; Science and Project of Chongqing Municipal Health Bureau ; National Natural Science Foundation of P.R. China ; Science and Project of Chongqing Municipal Health Bureau
研究领域[WOS]Oncology
关键词[WOS]HIPPO SIGNALING PATHWAY ; DROSOPHILA TUMOR-SUPPRESSOR ; HUMAN-BREAST CANCERS ; SOFT-TISSUE SARCOMA ; PROMOTER HYPERMETHYLATION ; DOWN-REGULATION ; GASTRIC-CANCER ; KIDNEY CANCER ; GENE ; EXPRESSION
英文摘要

Large tumor suppressor 1 (LATS1) gene is one of the key factors in Hippo signaling pathway. Inactivation of LATS1 by promoter methylation was found in colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), astrocytoma, breast cancer and it was proved to be a tumor suppressor. However, its role is unclear in renal cell carcinoma (RCC). In this study, the expression of LATS1 was determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry in 30 pairs of RCC tissues and matched normal kidney tissues and RCC cells. We found that the expression of LATS1 was markedly reduced in RCC tissues and cells, in the RCC tissue in 46.7% (14/30), while in the normal kidney tissues in 76.7% (23/30), and was associated with pathological grade and clinical stage of RCC. We detected methylation status of LATS1 by bisulfite sequence-PCR (BSP) in renal cancer cell line 786-O which lowers expression of LATS1, and we found it hypermethylated (in 97.5%). In addition, pharmacological demethylation using 5-Aza-2′-deoxycytidine (5-Aza) restored the expression of LATS1 mRNA and protein in 786-O cells, both LATS1 demethylation and overexpression of LATS1 downregulated the expression of Yes-associated protein (YAP), inhibited cell proliferation, induced cell apoptosis and cell cycle G1 arrest in 786-O cells. Thus, this report for the first time demonstrates the inactivation of LATS1 by promoter methylation and it is a tumor suppressor in kidney cancer. LATS1 may serve as a biomarker for possible early diagnosis and as a potential therapeutic target for human RCC.

语种英语
所属项目编号30972999 ; 2013-2-082
资助者National Natural Science Foundation of P.R. China ; Science and Project of Chongqing Municipal Health Bureau ; National Natural Science Foundation of P.R. China ; Science and Project of Chongqing Municipal Health Bureau
WOS记录号WOS:000344200700037
引用统计
被引频次:4[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/400002259/58037
专题北京大学第一临床医学院_泌尿外科
作者单位1.Peking Univ, Hosp 1, Inst Urol, Beijing, Peoples R China
2.Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400016, Peoples R China
3.Chongqing Med Univ, Univ Town Hosp, Gastroenterol & Neurol Ctr, Chongqing, Peoples R China
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GB/T 7714
Chen, Ke-Hong,He, Jiang,Wang, De-Lin,et al. Methylation-associated inactivation of LATS1 and its effect on demethylation or overexpression on YAP and cell biological function in human renal cell carcinoma[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2014,45(6):2511-2521.
APA Chen, Ke-Hong.,He, Jiang.,Wang, De-Lin.,Cao, Jian-Jia.,Li, Mei-Cai.,...&Liu, Wu-Jiang.(2014).Methylation-associated inactivation of LATS1 and its effect on demethylation or overexpression on YAP and cell biological function in human renal cell carcinoma.INTERNATIONAL JOURNAL OF ONCOLOGY,45(6),2511-2521.
MLA Chen, Ke-Hong,et al."Methylation-associated inactivation of LATS1 and its effect on demethylation or overexpression on YAP and cell biological function in human renal cell carcinoma".INTERNATIONAL JOURNAL OF ONCOLOGY 45.6(2014):2511-2521.
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