MicroRNAs (miRNAs) regulate diverse cancer hallmarks through sequence-specific regulation of gene expression, so genetic variability in their seed sequences or target sites could be responsible for cancer initiation or progression. While several efforts have been made to predict the locations of single nucleotide variants (SNVs) at miRNA target sites and associate them with cancer risk and susceptibility, there have been few direct assessments of SNVs in both mature miRNAs and their target sites to assess their impact on miRNA function in cancers. Using genome-wide target capture of miRNAs and miRNA-binding sites followed by deep sequencing in prostate cancer cell lines, here we identified prostate cancer-specific SNVs in mature miRNAs and their target binding sites. SNV rs9860655 in the mature sequence of miR-570 was not present in benign prostate hyperplasia (BPH) tissue or cell lines but was detectable in clinical prostate cancer tissue samples and adjacent normal tissue. SLC45A3 (prostein), a putative oncogene target of miR-1178, was highly upregulated in PC3 cells harboring an miR-1178 seed sequence SNV. Finally, systematic assessment of losses and gains of miRNA targets through 3′UTR SNVs revealed SNV-associated changes in target oncogene and tumor suppressor gene expression that might be associated with prostate carcinogenesis. Further work is required to systematically assess the functional effects of miRNA SNVs.

MicroRNAs (miRNAs) 通过基因表达的序列特异性调节来调节多种癌症标志，因此其种子序列或靶位点的遗传变异性可能是癌症发生或进展的原因。虽然已经做出了一些努力来预测 miRNA 靶位点的单核苷酸变体 (SNV) 的位置，并将它们与癌症风险和易感性联系起来，但几乎没有直接评估成熟 miRNA 及其靶位点中的 SNV 以评估其影响miRNA在癌症中的功能。使用全基因组目标捕获 miRNA 和 miRNA 结合位点，然后在前列腺癌细胞系中进行深度测序，我们在这里鉴定了成熟 miRNA 及其靶结合位点中的前列腺癌特异性 SNV。SLC45A3 (prostein) 是 miR-1178 的推定癌基因靶标，在具有 miR-1178 种子序列 SNV 的 PC3 细胞中高度上调。最后，通过 3'UTR SNV 对 miRNA 靶标的损失和获得的系统评估揭示了靶癌基因和肿瘤抑制基因表达的 SNV 相关变化，这可能与前列腺癌发生有关。需要进一步的工作来系统地评估 miRNA SNV 的功能效应。