Ella Institute of Melanoma, Sheba Medical Center, Ramat-Gan, Israel.
PLoS One. 2011;6(11):e27400. doi: 10.1371/journal.pone.0027400. Epub 2011 Nov 9.
Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3'UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3'UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3'UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation.
微小 RNA（miRNAs）是一种小的非编码 RNA，可在转录后水平调节基因产物。据认为，miRNAs 失去对细胞的调节作用支持了癌症的发展。基于黑色素瘤肿瘤的全基因组测序，我们使用三种不同的计算算法预测，黑色素瘤体细胞突变会全局降低 miRNA 与突变 3'UTR 的结合。这种现象反映了特征性的 UV 诱导突变的性质，即 C 到 T 的转换。此外，我们表明种子区域富含鸟嘌呤，从而使 miRNA 易于与 UV 突变的 3'UTR 结合减少。因此，非 UV 诱导的恶性肿瘤（例如肺癌和白血病）的突变模式不会产生类似的预测。据推测，UV 诱导的 miRNA 介导的基因调控中断在致癌作用中起作用。值得注意的是，深色皮肤人群中的 3'UTR SNPs 的 GC 含量明显高于浅色皮肤人群，这意味着在 UV 辐射过多的情况下，存在通过反式作用寡核苷酸来保存调节的进化压力。
