Abstract
PurposeTo investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3′-UTR SNP (1010A/G), which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer.MethodsExpression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G) was found located within the microRNA-7 binding site in the 3′-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G) frequency and clinical features in 391 cases.ResultsHOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G), located within the microRNA-7 binding site in the 3′-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage.ConclusionHOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G) located within 3′-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer.
Highlights
Urinary bladder cancer is the most common urological tumor in China [1]; the mechanisms of bladder cancer tumorigenesis have not been well illustrated
We have shown that this SNP could affect the expression of HOXB5 mainly by interfering with the function of miRNA-7 and SNP-related mRNA stability; the frequency of 1010G genotype was higher in cancer group compared to normal controls, and was found to be correlated with the risk of high grade and high stage
HOXB5 was Over-expressed in Human Bladder Cancer Tissues and Cell Lines
Summary
Urinary bladder cancer is the most common urological tumor in China [1]; the mechanisms of bladder cancer tumorigenesis have not been well illustrated. Data show that most of the bladder cancers are induced by carcinogens that damage the DNA. The sensitivity of the transitional epithelium’s microenvironment may be another important factor during tumorigenesis [2]. Oncogenes and tumor suppressors have been reported to play important roles in bladder cancer [3]. Genetic changes including SNPs, deletions, insertions, and changes of DNA copy number have been found to be involved in bladder carcinogenesis. A homeobox (HOX) is a sequence of about 180 nucleotides within genes that code for a protein domain called homeodomain. Studies showed that HOX genes constitute as much as
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