Toledo-Stuardo Karen, Ribeiro Carolina H, Campos Ivo, Tello Samantha, Latorre Yesenia, Altamirano Claudia, Dubois-Camacho Karen, Molina Maria Carmen
Faculty of Medicine, Immunology Program, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago, Chile.
School of Biochemical Engineering, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
Front Genet. 2023 Dec 7;14:1273296. doi: 10.3389/fgene.2023.1273296. eCollection 2023.
MicroRNAs (miRNAs) are small non-coding RNAs that participate as powerful genetic regulators. MiRNAs can interfere with cellular processes by interacting with a broad spectrum of target genes under physiological and pathological states, including cancer development and progression. Major histocompatibility complex major histocompatibility complex class I-related chain A (MICA) belongs to a family of proteins that bind the natural-killer group 2, member D (NKG2D) receptor on Natural Killer cells and other cytotoxic lymphocytes. MICA plays a crucial role in the host's innate immune response to several disease settings, including cancer. harbors various single nucleotide polymorphisms (SNPs) located in its 3'-untranslated region (3'UTR), a characteristic that increases the complexity of MICA regulation, favoring its post-transcriptional modulation by miRNAs under physiological and pathological conditions. Here, we conducted an in-depth analysis of 3'UTR sequences according to each allele described to date using NCBI database. We also systematically evaluated interactions between miRNAs and their putative targets on 3'UTR containing SNPs using analysis. Our results showed that SNPs rs9266829, rs 1880, and rs9266825, located in the target sequence of miRNAs hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-93, hsa-miR-1207.5p, and hsa-miR-711 could modify the binding free energy between -8.62 and -18.14 kcal/mol, which may affect the regulation of MICA expression. We believe that our results may provide a starting point for further exploration of miRNA regulatory effects depending on MICA allelic variability; they may also be a guide to conduct miRNA analysis for other highly polymorphic genes.
微小RNA(miRNA)是一类小的非编码RNA,作为强大的基因调节因子发挥作用。miRNA可通过在生理和病理状态下与广泛的靶基因相互作用来干扰细胞过程,包括癌症的发生和发展。主要组织相容性复合体I类相关链A(MICA)属于一类蛋白质家族,可与自然杀伤细胞和其他细胞毒性淋巴细胞上的自然杀伤细胞组2成员D(NKG2D)受体结合。MICA在宿主对包括癌症在内的多种疾病状态的先天免疫反应中起关键作用。其3'-非翻译区(3'UTR)存在各种单核苷酸多态性(SNP),这一特征增加了MICA调节的复杂性,有利于在生理和病理条件下通过miRNA对其进行转录后调控。在此,我们根据迄今使用NCBI数据库描述的每个等位基因,对3'UTR序列进行了深入分析。我们还使用分析系统评估了miRNA与其在含有SNP的3'UTR上的推定靶标之间的相互作用。我们的结果表明,位于miRNA hsa-miR-106a-5p、hsa-miR-17-5p、hsa-miR-20a-5p、hsa-miR-20b-5p、hsa-miR-93、hsa-miR-1207.5p和hsa-miR-711靶序列中的SNP rs9266829、rs1880和rs9266825可将结合自由能改变在-8.62至-18.14千卡/摩尔之间,这可能影响MICA表达的调控。我们相信,我们的结果可能为进一步探索依赖于MICA等位基因变异性的miRNA调节作用提供一个起点;它们也可能是对其他高度多态性基因进行miRNA分析的指南。