A microRNA-7 binding site polymorphism in HOXB5 leads to differential gene expression in bladder cancer.
A microRNA-7 binding site polymorphism in HOXB5 leads to differential gene expression in bladder cancer.
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HOXB5 中的 MicroRNA-7 结合位点多态性导致膀胱癌基因表达差异
DOI：
10.1371/journal.pone.0040127
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lin T
中科院分区：
文献类型：
--
作者：
Luo J;Cai Q;Wang W;Huang H;Zeng H;He W;Deng W;Yu H;Chan E;Ng CF;Huang J;Lin T
探讨HOXB 5在膀胱癌中的生物学功能，以及HOXB 5 3′-UTR SNP（1010 A/G）与膀胱癌临床特征的关系。应用实时荧光定量PCR和免疫组化方法检测35例膀胱癌组织和8株膀胱癌细胞系中HOXB 5的表达。接下来，我们使用细胞增殖、迁移和集落形成测定在体外探索HOXB 5的生物学功能。使用生物信息学，发现HOXB 5 3 '-UTR中的microRNA-7结合位点内存在一个SNP（1010 A/G）。实时荧光定量PCR检测不同等位基因对HOXB 5表达的影响。最后，采用多因素Logistic回归分析391例患者的SNP（1010 A/G）频率与临床特征的关系。HOXB 5在膀胱癌组织和细胞系中频繁过表达。HOXB 5的抑制抑制了癌细胞的致癌功能。接下来，我们证明了位于HOXB 5 3′-UTR的microRNA-7结合位点内的SNP（1010 A/G）可以主要通过microRNA-7的差异结合活性和SNP相关的mRNA稳定性来影响HOXB 5在膀胱癌中的表达。最后，我们还发现1010 G基因型在癌症组中的频率高于正常对照组，并且与高级别和高阶段的风险相关。HOXB 5在膀胱癌中过表达。HOXB 5基因3′-UTR内的一个miRNA结合SNP（1010 A/G）与基因表达相关，可能是膀胱癌的一个有希望的预后因子。
To 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. Expression 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. HOXB5 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. HOXB5 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.
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