Genetic variations in microRNAs and the risk and survival of renal cell cancer
Menée initialement sur 355 cas de carcinome à cellules rénales et 362 témoins, puis validée sur 647 cas et 660 témoins, cette étude identifie des polymorphismes à simple nucléotide, notamment dans le gène du micro-ARN196a2, en association avec la susceptibilité à ce type de cancer et avec le pronostic de la maladie
MicroRNAs (miRNAs) are a class of short non-coding, single stranded RNAs, which perform post-transcriptional regulatory functions as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) genes are currently being identified for contributing to cancer risk, prognosis and survival. We investigated whether genetic variations of miRNAs were associated with the risk and prognosis of renal cell carcinoma (RCC). We genotyped four common miRNA SNPs (i.e., miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444) to assess their associations with RCC risk in a two-stage case-control study (355 cases and 362 controls in discovery set, meanwhile 647 cases and 660 controls in validation set), as well as RCC survival in 311 patients. We found that the miR-196a2 SNP rs11614913 was associated with RCC susceptibility in recessive model (CC vs. TT/TC, adjusted OR = 0.65, 95% CI = 0.52-0.83) and with survival of RCC in dominant model (TC/CC vs. TT, adjusted HR = 0.40, 95% CI = 0.18-0.89). Meanwhile, the rs11614913 CC genotype was associated with the significantly decreased expression of miR-196a-5p in 26 renal cancer tissues (P = 0.018). Moreover, luciferase reporter assays revealed the potential effect of rs11614913 SNP on the binding of miR-196a-3p to its targets. These results suggested that the miR-196a2 rs11614913 may contribute to the genetic susceptibility and prognosis for RCC, which may act as a biomarker for RCC occurrence and prognosis.
http://carcin.oxfordjournals.org/content/early/2014/03/28/carcin.bgu082.abstract