MicroRNAs play a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope of miRNA post-transcriptional regulation. Our study investigated the relationship between cis-acting single-nucleotide polymorphisms (SNPs) in precursor miRNA regions and isomiR composition, represented by the ratio of a specific 5′-isomiR subtype to all isomiRs identified for a particular mature miRNA. Significant associations between 95 SNP–isomiR pairs were identified. Of note, rs6505162 was significantly associated with both the 5′-extension of hsa-miR-423-3p and the 5′-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that the expression of both isomiRs was significantly higher in tumors than in normal tissues. This study sheds light on the genetic regulation of isomiR maturation and advances our understanding of post-transcriptional regulation by microRNAs.
MicroRNAs在转录后基因表达调控中发挥关键作用。成熟microRNA序列的变异体（即isomiRs）源于前体加工过程中的非精确切割及核苷酸替换或添加。这些isomiRs能够靶向不同的mRNA或与其经典序列形成竞争关系，从而拓展了miRNA转录后调控的维度。本研究探讨了前体miRNA区域顺式作用单核苷酸多态性（SNPs）与isomiR组成特征（以特定成熟miRNA中某类5′-isomiR亚型占所有检测到isomiR的比例表示）的关联性，共鉴定出95个SNP-isomiR显著关联对。值得注意的是，rs6505162同时与hsa-miR-423-3p的5′端延伸型及hsa-miR-423-5p的5′端截短型isomiR存在显著关联。通过比较乳腺癌与正常组织样本，发现这两种isomiR在肿瘤组织中的表达量均显著高于正常组织。本研究揭示了isomiR成熟过程的遗传调控机制，深化了对microRNA转录后调控的理解。
肿瘤(癌症)患者之家