Investigative Role of Pre-MicroRNAs in Bladder Cancer Patients: A Case-Control Study in North India
Investigative Role of Pre-MicroRNAs in Bladder Cancer Patients: A Case-Control Study in North India
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DOI：
10.1089/dna.2010.1159
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发表时间：
2011-06-01
影响因子：
3.1
通讯作者：
Kapoor, Rakesh
中科院分区：
文献类型：
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作者：
Mittal, Rama Devi;Gangwar, Ruchika;Kapoor, Rakesh
MicroRNA（miRNA）是一类非编码RNA小分子，通过转录后调节靶基因参与多种细胞功能。前体miRNA基因中常见的遗传变异（单核苷酸多态性，SNP）可能会改变它们的表达和/或成熟，影响数千种靶mRNA，导致不同的功能后果。研究前体miRNA中的三种常见SNP（hsa-mir-146 a G>C rs 2910164、hsa-mir-196 a2 C>T rs 11614913和hsa-mir-499 T>C rs3746444）以评估它们与膀胱癌风险的关联。这项以医院为基础的病例对照研究包括212例经组织学证实的膀胱癌患者和250例健康对照，这些患者无关，种族相似，年龄和性别匹配。采用聚合酶链反应-限制性片段长度多态性方法进行基因分型。我们的研究结果表明，rs 11614913的杂合基因型在病例组中高于对照组，但结果略有显着性（p = 0.055;比值比，1.44）。吸烟对调节所研究的三种miRNA SNP中的任何一种的作用都没有影响。在膀胱癌患者中未观察到与肿瘤分期或分级的相关性。尽管携带所研究的三种miRNA的变异基因型的个体与膀胱癌风险之间没有关联，但rs 11614913中异质性的边缘显著性表明在不同种族的大队列中进一步表征了miRNA SNP。这可能进一步为了解miRNAs与疾病病因之间的潜在机制提供新的前景。
MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of cellular functions through post-transcriptional regulations on target genes. Common genetic variants (single-nucleotide polymorphisms, SNPs) in pre-miRNA genes may alter their expression and/or maturation effecting thousands of target mRNAs, resulting in varied functional consequences. Three common SNPs (hsa-mir-146a G>C rs2910164, hsa-mir-196a2 C>T rs11614913, and hsa-mir-499 T>C rs3746444) in pre-miRNAs were investigated to evaluate their association with urinary bladder cancer risk. The hospital-based case-control study comprised of 212 histologically confirmed patients with urinary bladder cancer and 250 healthy controls who were unrelated, of similar ethnicity, and age and gender matched. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism methodology. Our results showed that the heterozygous genotype of rs11614913 was higher in cases than controls but the results were marginally significant (p = 0.055; odds ratio, 1.44). Smoking had no impact in modulating the effect of any of the three miRNA SNPs studied. No association was observed with either the tumor stage or grade in patients with bladder cancer. Even though there was no association between the individuals carrying the variant genotypes of the three miRNA studied and bladder cancer risk, marginal significance of heterozygousity in rs11614913 suggested further characterization of miRNA SNPs in a large cohort of varied ethnicity. This could further provide new prospects for understanding the underlying mechanisms between miRNAs and disease etiology.