影响乙型肝炎感染的MicroRNA相关单核苷酸的计算分析。

Mirza Ali Nazarnezhad, Mahdi Barazesh, Soudabeh Kavousipour, Shiva Mohammadi, Ebrahim Eftekhar, Sajad Jalili
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引用次数: 0

摘要

背景:MicroRNAs (miRNAs)通过靶向基因表达所需的细胞转录因子或直接结合HBV转录物,在乙型肝炎病毒(HBV)感染及其并发症中起着关键作用。miRNA基因的单核苷酸多态性(snp)影响其表达和靶基因的调控、HBV感染的临床过程、诊断和治疗干预。方法:应用miRNA SNP3.0软件等多种通用数据集,通过注释snp对mRNA-miRNA和miRNA- rbs (miRNA结合位点)相互作用的功能影响,筛选直接或间接通过hbv感染调控mRNA转录物的miRNA基因多态性的计算评估和编目。结果:139个影响乙型肝炎感染的mirna中检测到2987个snp。其中,313个snp被预测在乙型肝炎感染的进展中起重要作用。计算分析还显示,313个snp中有45个位于种子区,比其他snp更重要。哈斯- mir -139-3p在种子区拥有最多的snp (n=6)。另一方面,癌症蛋白聚糖、粘附体连接、赖氨酸降解、NFkappa B信号级联、ecm受体结合、病毒致癌、脂肪酸代谢、tgf - β信号通路、p53信号通路、免疫逃避相关通路和脂肪酸生物合成是这139种mirna影响的最重要途径。结论:25个miRNA种子区的45个snp可作为调控乙型肝炎感染的miRNA基因目录。研究结果还表明,这些mirna调控的最重要的途径可以用于治疗目的。
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The Computational Analysis of Single Nucleotide Associated with MicroRNA Affecting Hepatitis B Infection.

Background: MicroRNAs (miRNAs) have a pivotal role in Hepatitis B Virus (HBV) infection and its complications by targeting the cellular transcription factors required for gene expression or directly binding to HBV transcripts. Single Nucleotide Polymorphisms (SNPs) in miRNA genes affect their expression and the regulation of target genes, clinical course, diagnosis, and therapeutic interventions of HBV infection.

Methods: Computational assessment and cataloging of miRNA gene polymorphisms targeting mRNA transcripts straightly or indirectly through the regulation of hepatitis B infection by annotating the functional impact of SNPs on mRNA-miRNA and miRNA-RBS (miRNA binding sites) interaction were screened by applying various universally available datasets such as the miRNA SNP3.0 software.

Results: 2987 SNPs were detected in 139 miRNAs affecting hepatitis B infection. Among them, 313 SNPs were predicted to have a significant role in the progression of hepatitis B infection. The computational analysis also revealed that 45 out of the 313 SNPs were located in the seed region and were more important than others. Has-miR-139-3p had the largest number of SNPs in the seed region (n=6). On the other hand, proteoglycans in cancer, adherens junction, lysine degradation, NFkappa B signaling cascade, ECM-receptor binding, viral carcinogenesis, fatty acid metabolism, TGF-beta signaling pathway, p53 signaling pathway, immune evasion related pathways, and fatty acid biosynthesis were the most important pathways affected by these 139 miRNAs.

Conclusion: The results revealed 45 SNPs in the seed region of 25 miRNAs as the catalog in miRNA genes that regulated the hepatitis B infection. The results also showed the most important pathways regulated by these miRNAs that can be targeted for therapeutic purposes.

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