Al-Asadi Sura, Mansour Hiba, Ataimish Ahmed Jwaid, Al-Kahachi Rusul, Rampurawala Jamila
College of Health and Medical Techniques, Middle Technical University, Baghdad, Iraq.
College of Pharmacy, Baghdad University, Baghdad, Iraq.
Bioinform Biol Insights. 2023 Sep 9;17:11779322231193535. doi: 10.1177/11779322231193535. eCollection 2023.
Tumor microenvironment is characterized by the occurrence of significant changes due to disrupted signaling pathways that affect a broad spectrum of cellular activities such as proliferation, differentiation, signaling, invasiveness, migration, and apoptosis. Similarly, a downregulated suppressor of cytokine signaling 3 (SOCS3) promotes increased JAK/STAT function due to aberrant cytokine signaling, which results in increased cell proliferation, differentiation, and migration. Multiple carcinomas including breast cancer, prostate cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer involve the disruption of SOCS3 expression due to microRNA overexpression. MicroRNAs are small, conserved, and non-coding RNA molecules that regulate gene expression through post-transcriptional inhibition and mRNA destabilization. The aim of this study was to identify putative microRNAs that interact with SOCS3 and downregulate its expression. In this study, miRWalk, TargetScan, and miRDB were used to identify microRNAs that interact with SOCS3, whereas RNA22 was utilized to identify the binding sites of 238 significant microRNAs. The tertiary structures of shortlisted microRNAs and SOCS3 regions were predicted through MC Sym and RNAComposer, respectively. For molecular docking, HDOCK was used, which predicted 80 microRNA-messengerRNA complexes and the interactions of the top 5 shortlisted complexes were assessed. The complexes were shortlisted on the basis of least binding affinity score and maximum confidence score. This study identifies the interactions of known (miR-203a-5p) and novel (miR-6756-5p, miR-6732-5p, miR-1203, miR-6887-5p) microRNAs with SOCS3 regions due to their maximum interactions. Identifying the interactions of these microRNAs with SOCS3 will significantly advance the understanding of oncomiRs (miRNAs that are associated with cancer development) in tumor development due to their influence on SOCS3 expression. These insights will assist in future studies to understand the significance of miRNA-SOCS3-associated tumor development and progression.
肿瘤微环境的特征是由于信号通路的破坏而发生显著变化，这些信号通路影响广泛的细胞活动，如增殖、分化、信号传导、侵袭、迁移和凋亡。同样，细胞因子信号转导抑制因子3（SOCS3）的下调会因异常的细胞因子信号传导而促进JAK/STAT功能增强，从而导致细胞增殖、分化和迁移增加。包括乳腺癌、前列腺癌、肝细胞癌、胰腺癌和结直肠癌在内的多种癌症都因微小RNA的过表达而导致SOCS3表达受到破坏。微小RNA是小的、保守的非编码RNA分子，它们通过转录后抑制和mRNA不稳定来调节基因表达。本研究的目的是鉴定与SOCS3相互作用并下调其表达的假定微小RNA。在本研究中，使用miRWalk、TargetScan和miRDB来鉴定与SOCS3相互作用的微小RNA，而利用RNA22来鉴定238个重要微小RNA的结合位点。分别通过MC Sym和RNAComposer预测入围微小RNA和SOCS3区域的三级结构。对于分子对接，使用HDOCK，其预测了80个微小RNA-信使RNA复合物，并评估了排名前5的入围复合物的相互作用。根据最低结合亲和力得分和最高置信度得分对复合物进行入围筛选。本研究确定了已知的（miR-203a-5p）和新的（miR-6756-5p、miR-6732-5p、miR-1203、miR-6887-5p）微小RNA与SOCS3区域的相互作用，因为它们之间的相互作用最强。确定这些微小RNA与SOCS3的相互作用将显著推进对肿瘤发生过程中癌基因miRNA（与癌症发展相关的miRNA）的理解，因为它们会影响SOCS3的表达。这些见解将有助于未来的研究理解与miRNA-SOCS3相关的肿瘤发展和进展的意义。
