Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Physiol. 2020 Feb;235(2):966-978. doi: 10.1002/jcp.29012. Epub 2019 Jul 25.
Esophageal squamous cell carcinoma (ESCC) is the dominant histological type of esophageal cancer significantly reported in developing nations. There is an increasing evidence suggesting that single nucleotide polymorphisms (SNPs) in the untranslated regions of genes (3'-UTRs) targeted by microRNAs (miRNAs) can change the target gene's expression and thereby affect the individual's cancer risk. Thus, in support of the role of SNPs occurring in miRNA target sites (miR-TS-SNPs) in the cancer, we analyzed the next generation sequencing data of 10 ESCC patients. In each patient, about 3,000 SNPs in 3'-UTRs were obtained in their whole-exome sequencing profiles. We applied two separate methods, manual and computational in silico approaches, to predict the miR-TS-SNPs with more effects on the miRNA-target interactions. dbSNP, 1000G, ExAC, Iranome, miRandb, miRCancer, TargetScan, Human, miRNASNP2 and miRBase databases were used for positive selection of miR-TS-SNPs and DIANA-miRPath v3.0 for pathway analysis. We identified six rare germline miR-TS-SNPs and two other ones with unknown miR-TS-SNPs. We interestingly observed all of these variants in only one patient, which can be evidence of the relationship between miR-TS-SNPs and cancer incidence. The study of cancer genetics including miR-TS-SNPs reveals miRNAs and their related pathways, which will be greatly useful in cancer research from noninvasive biomarkers to new treatments.
食管鳞状细胞癌（ESCC）是发展中国家主要报道的食管癌组织学类型。越来越多的证据表明，miRNA 靶向基因的非翻译区（3'-UTRs）中的单核苷酸多态性（SNPs）可以改变靶基因的表达，从而影响个体的癌症风险。因此，为了支持 miRNA 靶位点（miR-TS-SNPs）在癌症中发生的 SNP 的作用，我们分析了 10 名 ESCC 患者的下一代测序数据。在每个患者中，在其全外显子测序图谱中获得了大约 3000 个 3'-UTR 中的 SNPs。我们应用了两种独立的方法，手动和计算的计算机模拟方法，来预测对 miRNA 靶相互作用有更多影响的 miR-TS-SNPs。dbSNP、1000G、ExAC、Iranome、miRandb、miRCancer、TargetScan、Human、miRNASNP2 和 miRBase 数据库用于 miR-TS-SNPs 的阳性选择，而 DIANA-miRPath v3.0 用于通路分析。我们鉴定了六个罕见的种系 miR-TS-SNPs 和另外两个未知的 miR-TS-SNPs。我们有趣地观察到所有这些变体仅存在于一个患者中，这可能是 miR-TS-SNPs 与癌症发病率之间关系的证据。包括 miR-TS-SNPs 的癌症遗传学研究揭示了 miRNAs 及其相关通路，这将对癌症研究非常有用，从非侵入性生物标志物到新的治疗方法。
