Epigenetic inactivation of HOXA11, a novel functional tumor suppressor for renal cell carcinoma, is associated with RCC TNM classification

Autor: Jindong Sheng, Yu Fan, Qian Zhang, Yang Yang, Jie Jin, Yun Cui, Guanyu Kuang, Lu Wang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Lu Wang 1, 3 , Yun Cui 1 , Jindong Sheng 1 , Yang Yang 1 , Guanyu Kuang 1 , Yu Fan 1, 2 , Jie Jin 1 , Qian Zhang 1 1 Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China 2 Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital, Beijing 100034, China 3 Department of Urology, National Urological Cancer Center, Peking University First Hospital, Beijing 100034, China Correspondence to: Qian Zhang, email: zhangqian@bjmu.edu.cn Jie Jin, email: jinjie@vip.163.com Keywords: HOXA11, methylation, renal cell carcinoma Received: August 08, 2016 Accepted: January 16, 2017 Published: February 24, 2017 ABSTRACT Epigenetic inactivation of HOXA11 , a putative tumor suppressor, is frequently observed in a number of solid tumors, but has not been described in RCC (renal cell carcinoma). In this study, we investigated the expression, epigenetic changes and the function of HOXA11 in human renal cell carcinoma (RCC). HOXA11 was silenced or down-regulated in RCC cell lines and tissues. Methylation specific PCR (MSP) and bisulfite genomic sequencing (BGS) revealed that the HOXA11 promoter was hypermethylated in 5/6 RCC cell lines. Demethylation treatment resulted in demethylation of the promoter and increased HOXA11 expression in these cell lines. HOXA11 methylation was also detected in 68/95 (70.5%) primary RCC tumors, but only rare adjacent non-malignant renal tissues (13%, 3/23) showed hypermethylation of promoter. We also found that the methylation of HOXA11 was associated with higher TNM classification of RCC ( p
Databáze: OpenAIRE