Table_4_A Systematic Review of Candidate miRNAs, Its Targeted Genes and Pathways in Chronic Myeloid Leukemia–An Integrated Bioinformatical Analysis.xlsx

Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully used to treat CML, there are still cases of resistance. The resistance occurred mainly due to the mutation in the tyrosine kinase domain of the BCR-ABL1 gene. However, there are still many cases with unknown causes of resistance as the etiopathology of CML are not fully understood. Thus, it is crucial to figure out the complete pathogenesis of CML, and miRNA can be one of the essential pathogeneses. The objective of this study was to systematically review the literature on miRNAs that were differentially expressed in CML cases. Their target genes and downstream genes were also explored. An electronic search was performed via PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct. The following MeSH (Medical Subject Heading) terms were used: chronic myeloid leukaemia, genes and microRNAs in the title or abstract. From 806 studies retrieved from the search, only clinical studies with in-vitro experimental evidence on the target genes of the studied miRNAs in CML cells were included. Two independent reviewers independently scrutinised the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. Study design, sample size, sampling type, and the molecular method used were identified for each study. The pooled miRNAs were analysed using DIANA tools, and target genes were analysed with DAVID, STRING and Cytoscape MCODE. Fourteen original research articles on miRNAs in CML were included, 26 validated downstream genes and 187 predicted target genes were analysed and clustered into 7 clusters. Through GO analysis, miRNAs’ target genes were localised throughout the cells, including the extracellular region, cytosol, and nucleus. Those genes are involved in various pathways that regulate genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration of CML cells.

慢性髓细胞性白血病，一种由相互易位引起的血液系统恶性肿瘤，其根本病因为BCR-ABL1癌基因的产生。尽管酪氨酸激酶抑制剂已被成功应用于治疗慢性髓细胞性白血病，但仍有部分病例出现耐药现象。此类耐药性主要源于BCR-ABL1基因酪氨酸激酶域的突变。然而，由于慢性髓细胞性白血病的病因病理学尚未完全明了，仍有大量耐药病例原因不明。因此，揭示慢性髓细胞性白血病的完整发病机制至关重要，而miRNA可能是其中的关键环节之一。本研究旨在系统性地回顾关于慢性髓细胞性白血病病例中差异表达miRNA的文献，并探究其靶基因及下游基因。通过PubMed、Scopus、EBSCOhost MEDLINE和Science Direct等数据库进行电子检索，使用以下医学主题词进行检索：慢性髓细胞性白血病、标题或摘要中包含基因和microRNA。从检索到的806篇研究中，仅纳入了具有针对所研究miRNA靶基因在慢性髓细胞性白血病细胞中体外实验证据的临床研究。两位独立审稿人独立审查了标题和摘要，以确定符合纳入标准的研究。对每项研究的设计、样本量、采样类型和分子方法进行了识别。利用DIANA工具分析了汇集的miRNA，并使用DAVID、STRING和Cytoscape MCODE分析了靶基因。共纳入了14篇关于慢性髓细胞性白血病miRNA的原研文章，分析了26个验证的下游基因和187个预测的靶基因，并将它们聚类为7个簇。通过GO分析，miRNA的靶基因被定位在细胞的不同区域，包括细胞外区域、细胞质和细胞核。这些基因参与了调节基因组不稳定、增殖、凋亡、细胞周期、分化和慢性髓细胞性白血病细胞迁移等多种通路。