Clinical Biochemistry, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
Clin Chem Lab Med. 2011 Sep 9;49(12):2073-80. doi: 10.1515/CCLM.2011.708.
The presence of sequence variants in miRNA genes may influence their processing, expression and binding to target mRNAs. Since single miRNA can have a large number of potential mRNA targets, even minor variations in its expression can have influences on hundreds of putative mRNAs.
Here, we evaluated 101 paired samples (cancer and normal tissues) from non-small cell lung carcinoma (NSCLC) patients to study the genotype distribution of single nucleotide polymorphisms (SNPs) in miR-146a (rs2910164 C-G), miR-149 (rs2292832 C-T), miR-196a2 (rs11614913 C-T) and miR-499 (rs3746444 G-A) and their influence on the expression of respective miRNAs.
Relative expression of miR-146a, miR-149 and miR-499 were comparable in NSCLC and in paired control tissues. On the contrary, we clearly detected a significant increase (p<0.001) of miR-196a2 expression in NSCLC. In particular we found a significant association between miR-196a2 CC genotype and high expression, whereas TT geno-type showed a very low expression in comparison to both CT (p<0.005) and CC patients (p<0.01). We did not find any association between miR-149, miR-196a2 and miR-499 genotype and risk of NSCLC. Conversely, CG genotype of miR-146a appeared associated to an increased risk for NSCLC (p=0.042 and 1.77 OR).
Our results seem to demonstrate that sequence variants of miR-196a2 can have an influence on its expression, while miR-146a can have a role in increasing the risk of NSCLC.
miRNA 基因中的序列变异可能影响其加工、表达和与靶 mRNA 的结合。由于单个 miRNA 可能有大量潜在的 mRNA 靶标，因此其表达的微小变化都可能对数百个假定的 mRNA 产生影响。
在这里，我们评估了 101 对非小细胞肺癌 (NSCLC) 患者的癌组织和正常组织样本，以研究 miR-146a(rs2910164C-G)、miR-149(rs2292832C-T)、miR-196a2(rs11614913C-T)和 miR-499(rs3746444G-A) 中单个核苷酸多态性 (SNP) 的基因型分布及其对各自 miRNA 表达的影响。
miR-146a、miR-149 和 miR-499 在 NSCLC 与配对对照组织中的相对表达水平相当。相反，我们清楚地检测到 miR-196a2 在 NSCLC 中的表达显著增加(p<0.001)。特别是，我们发现 miR-196a2 CC 基因型与高表达显著相关，而 TT 基因型与 CT(p<0.005)和 CC(p<0.01)患者相比表达非常低。我们没有发现 miR-149、miR-196a2 和 miR-499 基因型与 NSCLC 风险之间存在任何关联。相反，miR-146a 的 CG 基因型似乎与 NSCLC 的风险增加相关(p=0.042 和 1.77OR)。
我们的结果似乎表明，miR-196a2 的序列变异可能对其表达产生影响，而 miR-146a 可能在增加 NSCLC 的风险中起作用。
