Cipollini Monica, Landi Stefano, Gemignani Federica
Department of Biology, University of Pisa, Pisa, Italy.
Pharmgenomics Pers Med. 2014 Jul 23;7:173-91. doi: 10.2147/PGPM.S61693. eCollection 2014.
MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression. They have been implicated in a broad range of biological processes, and miRNA-related genetic alterations probably underlie several human diseases. Single nucleotide polymorphisms of transcripts may modulate the posttranscriptional regulation of gene expression by miRNAs and explain interindividual variability in cancer risk and in chemotherapy response. On the basis of recent association studies published in the literature, the present review mainly summarizes the potential role of miRNAs as molecular biomarkers for disease susceptibility, diagnosis, prognosis, and drug-response prediction in tumors. Many clues suggest a role for polymorphisms within the 3' untranslated regions of KRAS rs61764370, SET8 rs16917496, and MDM4 rs4245739 as SNPs in miRNA binding sites highly promising in the biology of human cancer. However, more studies are needed to better characterize the composite spectrum of genetic determinants for future use of markers in risk prediction and clinical management of diseases, heading toward personalized medicine.
微小RNA(miRNAs)是真核基因表达的重要调节因子。它们参与了广泛的生物学过程,与miRNA相关的基因改变可能是多种人类疾病的基础。转录本的单核苷酸多态性可能会调节miRNAs对基因表达的转录后调控,并解释个体在癌症风险和化疗反应方面的差异。基于文献中最近发表的关联研究,本综述主要总结了miRNAs作为肿瘤疾病易感性、诊断、预后及药物反应预测分子生物标志物的潜在作用。许多线索表明,KRAS rs61764370、SET8 rs16917496和MDM4 rs4245739的3'非翻译区内的多态性作为miRNA结合位点的单核苷酸多态性,在人类癌症生物学中具有很大潜力。然而,需要更多研究来更好地描绘遗传决定因素的综合图谱,以便将来在疾病风险预测和临床管理中使用这些标志物,朝着个性化医疗的方向发展。