Research Papers:

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

Lu Wang, Yun Cui, Jindong Sheng, Yang Yang, Guanyu Kuang, Yu Fan, Jie Jin and Qian Zhang _

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Oncotarget. 2017; 8:21861-21870. https://doi.org/10.18632/oncotarget.15668

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Lu Wang1,3, Yun Cui1, Jindong Sheng1, Yang Yang1, Guanyu Kuang1, Yu Fan1,2, Jie Jin1, Qian Zhang1

1Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China

2Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital, Beijing 100034, China

3Department of Urology, National Urological Cancer Center, Peking University First Hospital, Beijing 100034, China

Correspondence to:

Qian Zhang, email: [email protected]

Jie Jin, email: [email protected]

Keywords: HOXA11, methylation, renal cell carcinoma

Received: August 08, 2016     Accepted: January 16, 2017     Published: February 24, 2017


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<0.05). Ectopic expression of HOXA11 led to significant inhibition of proliferation, colony formation, migration and invasion abilities and induced RCC cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling. Thus, our study demonstrated that HOXA11 function as a tumor suppressor in RCC, while it is frequently silenced by promoter methylation in RCC.

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