Table_3_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.

慢性髓性白血病（Chronic myeloid leukaemia）系由相互易位引起之血液系统恶性肿瘤，其原因为BCR-ABL1癌基因的生成。尽管酪氨酸激酶抑制剂已成功应用于治疗慢性髓性白血病（CML），但仍存在耐药病例。耐药性主要源于BCR-ABL1基因酪氨酸激酶结构域的突变。然而，由于慢性髓性白血病的病因病理学尚未完全明了，故仍有许多耐药病例的成因不明。因此，阐明慢性髓性白血病的完整发病机制至关重要，其中miRNA（microRNA）可能是其关键发病机制之一。本研究旨在系统地回顾有关慢性髓性白血病病例中差异表达的miRNA的文献，并探讨其靶基因及下游基因。通过PubMed、Scopus、EBSCOhost MEDLINE和Science Direct等电子数据库进行检索，采用以下MeSH（医学主题词）术语：慢性髓性白血病、标题或摘要中提及的基因与microRNA。从检索到的806篇研究中，仅纳入了具有针对所研究miRNA的靶基因在慢性髓性白血病细胞中体外实验证据的临床研究。两名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、抽样类型以及所用的分子方法进行了识别。使用DIANA工具对汇总的miRNA进行分析，并利用DAVID、STRING和Cytoscape MCODE分析靶基因。纳入了14篇关于慢性髓性白血病miRNA的原创研究文章，分析了26个已验证的下游基因和187个预测的靶基因，并将它们聚类为7个簇。通过GO分析，miRNA的靶基因定位在细胞的不同部位，包括细胞外区域、细胞质和细胞核。这些基因参与调节基因组不稳定性、增殖、凋亡、细胞周期、分化和迁移等多种途径。