Effects of miR-SNPs in Cancer Susceptibility

MicroRNAs are important regulators of gene expression involved in physiological andpathological processes such as development and cancer. Alterations in miRNA expressionare also impact on the initiation, progression, and metastasis of human malignancy. Singlenucleotide polymorphisms (SNPs) are variations of DNA sequences which can causesusceptibility to cancer risk. Up to now, about 10 million SNPs found in the human genomethat usually occurs once in every 100 to 300 bp. Epidemiological studies have proven aconnection between variations in gene sequence, environmental interactions and cancerrisk, nevertheless, most SNPs are silent. SNPs could be affect miRNA functions and itsexpression level in several ways. First manner that SNPs affect the function of miRNAs areinfluencing the transcription level of primary transcript. In fact, SNPs in miRNA binding sitesof target genes leads to cancer development via reducing efficiency of miRNA binding to thetarget sites, blocking binding sites or create illegitimate miRNA target sites. Also, SNPs couldbe occurred in miRNA biogenesis pathway and influence pri-miRNA and pre-miRNAprocessing to mature miRNA sequence. These polymorphisms might alter expression andinteractions of proteins involved in miRNA biogenesis pathway. Many single nucleotidepolymorphisms have been identified in main components of the silencing machinery such asGEMIN4, GEMIN3, XPO5, AGO1, AGO2, TRBP and RAN which contribute to the geneticvariations and consequently cancer risk. miRNA-associated SNPs have a great potential tointerfere with the function of miRNAs which regulate genes involved in crucial signalingpathways and apoptosis or proliferation. As a result, miRNA-based SNPs including SNP inmiRNAs binding sites and the genes involved in their processing linked to cancersusceptibility, therapeutic effect, and prognosis.

Keywords:

MicroRNA , SNP , Prognosis , Cancer , Polymorphism