Login to Access Video or Poster Abstract: MP60-11
Sources of Funding: none

Introduction

HOXA11 is a member of HOX transcription factors, the HOX genes encode transcription factors that play an essential role in regulating cell differentiation and proliferation. The hypermethylation of HOXA11 promoter region has been reported in various cancers. However, the epigenetic alteration and function of HOXA11 in human renal cell carcinoma (RCC) has not been explained. Therefore, to investigate the expression and function of HOXA11 is significant.

Methods

PCR and IHC were used to check the expression of HOXA11 in RCC cells and tissues. To detect the methylation status of HOXA11 promoter, MSP (methylation specific PCR) and BGS (bisulfite genomic sequencing) were used. We also used colony formation, CCK8, wound healing, Transwell, Annexin V apoptosis assay and Western-blot to assess the function and related mechanism of HOXA11 in renal cell carcinoma. Finally, we used Fisher’s exact test, Student’s t test and Chi-square test to analyze the correlation between clinical features and HOXA11 promoter methylation.

Results

HOXA11 was down-regulated by promoter aberrant methylation in both RCC cell lines and tissues compared with normal kidney cell line and tissues. HOXA11 methylation was found at higher prevalence (70.5%, 68/95) in human RCC tissues than in adjacent non-malignant renal tissues (13%, 3/23) and associated with higher TNM classification of RCC (p<0.05). In addition, restoration of HOXA11 expression reduced the proliferation, colony formation, migration and invasion abilities and induced RCC cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling.

Conclusions

Our study demonstrated that HOXA11 function as a tumor suppressor in RCC which is mainly regulated by epigenetics.

Funding

none