Table_5_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，作为一种由相互易位引起的血液系统恶性肿瘤，其病源在于BCR-ABL1癌基因的产生。尽管酪氨酸激酶抑制剂在治疗慢性髓性白血病方面取得了显著成效，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，由于慢性髓性白血病的病因病理尚未完全明了，仍有大量耐药病例的原因不明。因此，阐明慢性髓性白血病的完整发病机制至关重要，而微RNA（miRNA）可能是其中关键环节之一。本研究旨在系统回顾有关慢性髓性白血病病例中差异表达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等数据库进行电子检索，采用以下医学主题词（MeSH）进行搜索：慢性髓性白血病、基因与微RNA在标题或摘要中。从检索到的806项研究中，仅纳入具有体外实验证据的临床研究，这些研究针对的miRNA靶基因在慢性髓性白血病细胞中的表达具有差异。两位独立的审稿人分别对标题和摘要进行了审查，以确定符合纳入标准的研究。对每项研究的设计、样本量、抽样类型以及所使用的分子方法进行了识别。使用DIANA工具对汇总的miRNA进行了分析，并利用DAVID、STRING和Cytoscape MCODE对靶基因进行了分析。共纳入14篇关于慢性髓性白血病miRNA的原创研究文章，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的靶基因被定位在整个细胞中，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、细胞凋亡、细胞周期、分化和迁移等慢性髓性白血病细胞的多种途径。