Srivastava Shruti, Singh Shalini, Fatima Naseem, Mittal Balraj, Srivastava Anand Narain
Ex-Senior Research Fellow, Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Professor, Department of Radiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
J Clin Diagn Res. 2017 Sep;11(9):GC01-GC04. doi: 10.7860/JCDR/2017/25361.10543. Epub 2017 Sep 1.
MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers.
The present study investigated the genetic variants in pre-miRNAs (hsa-miRNA-196a2 rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for their role in cervical cancer susceptibility.
The study comprised 164 controls and 184 patients of cervical cancer. The genotypic frequency of miRNA polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0.
Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically significant association with considerable risk for cervical cancer at genotypes (CC, p=0.001, OR=4.801) and variant allele (p<0.001, OR=2.307). MiRNA 146a and miRNA 196a2 polymorphisms showed no association with cervical cancer. However, interaction of miRNA polymorphisms with smoking habit showed higher risk of cervical cancer with miRNA 196a2 polymorphism in patients with smoking but no significant modification in the risk of cervical cancer was seen for other polymorphisms.
The results of the present study demonstrate that, miRNA 499 T/C polymorphism is significantly associated with genetic susceptibility to cervical cancer and may have a role in its pathogenesis.
微小RNA(miRNA)是短链(约22个核苷酸)的调节性RNA,可调节基因表达,且在包括癌症在内的多种疾病中表达异常。有人提出,前体miRNA(pre-miRNA)中的单核苷酸多态性可改变miRNA的加工、表达及其与靶mRNA的结合,代表了另一种类型的遗传变异性,可能导致人类癌症易感性增加。
本研究调查前体miRNA(hsa-miRNA-196a2 rs11614913 C/T、hsa-miRNA-499 rs3746444 T/C和hsa-miRNA-146a rs2910164 G/C)中的基因变异在宫颈癌易感性中的作用。
该研究包括164名对照者和184名宫颈癌患者。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法确定miRNA多态性的基因型频率。使用SPSS 15.0软件进行逻辑回归分析。
Hsa-miRNA-499 rs3746444 T/C多态性在基因型(CC,p=0.001,OR=4.801)和变异等位基因(p<0.001,OR=2.307)水平与宫颈癌发生风险显著相关。MiRNA 146a和miRNA 196a2多态性与宫颈癌无相关性。然而,miRNA多态性与吸烟习惯的相互作用显示,吸烟患者中miRNA 196a2多态性与宫颈癌风险较高相关,但其他多态性对宫颈癌风险无显著影响。
本研究结果表明,miRNA 499 T/C多态性与宫颈癌遗传易感性显著相关,可能在其发病机制中起作用。