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Updated: Sep 13, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
Published on: April 29, 2014
Epigenetic inactivation of HOXA11, a novel functional tumor suppressor for renal cell carcinoma, is associated with
Lu Wang1,2, Yun Cui1, Jindong Sheng1
1Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.
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<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.
Insights
HOXA11, a tumor suppressor, is frequently silenced by promoter methylation in renal cell carcinoma (RCC). Restoring HOXA11 expression inhibits RCC cell proliferation, migration, and invasion, confirming its tumor suppressor role in kidney cancer.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- HOXA11 is a potential tumor suppressor gene implicated in various solid tumors.
- Its role and epigenetic regulation in renal cell carcinoma (RCC) remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression, promoter methylation, and functional role of HOXA11 in human renal cell carcinoma (RCC).
Main Methods:
- Analysis of HOXA11 expression in RCC cell lines and tissues.
- Methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) to assess promoter methylation.
- Demethylation treatment to evaluate the effect on HOXA11 expression.
- Functional assays including proliferation, colony formation, migration, invasion, and apoptosis.
- Assessment of Wnt signaling pathway activity.
Main Results:
- HOXA11 was found to be silenced or downregulated in RCC cell lines and tissues.
- The HOXA11 promoter was hypermethylated in a majority of RCC cell lines (5/6) and primary tumors (70.5%).
- Demethylation treatment restored HOXA11 expression, and its methylation correlated with advanced TNM classification in RCC.
- Ectopic HOXA11 expression suppressed RCC cell proliferation, colony formation, migration, invasion, and induced apoptosis.
- HOXA11 was shown to inhibit the Wnt signaling pathway.
Conclusions:
- HOXA11 functions as a tumor suppressor in renal cell carcinoma.
- Frequent promoter hypermethylation leads to HOXA11 silencing in RCC, contributing to tumorigenesis.
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