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

Abstract

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.

The Mechanism of Anti-Tumor Activity of 6-Morpholino- and 6-Amino-9-Sulfonylpurine Derivatives on Human Leukemia Cells

“…Therefore, a decrease in miR-21 expression may be considered beneficial in promoting apoptosis and cell death. In the context of chronic myeloid leukemia (CML), miR-21 has been extensively studied as an important regulator of gene expression that may influence the efficacy of tyrosine kinase inhibitors (TKIs) commonly used in to treat CML [ 40 ]. Previous research by Alves et al has shown that low miR-21 levels at the time of CML diagnosis are associated with a better response to TKI therapy, making it an attractive target for drug therapy [ 41 ].…”

MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia

“…The importance of miRNAs in CLL prognosis has been investigated in various research. as well as other research groups, have examined miRNAs in CLL patients with overexpression of ZAP70 and unmutated IGHV gene; they reported a significant association between the overexpression of miR‐15a, miR‐16‐1, miR‐16‐2, miR‐23b, miR‐24‐1, miR‐146, miR‐155, miR‐195, miR‐221, and down‐expression of miR‐223, miR‐29a‐2, miR‐29b‐2, and miR‐29c with unmutated IGHV gene, high expression of ZAP70, and unfavorable prognostic in CLL cases [121‐123]. Another study conducted by Due et al.…”

Evaluation of MicroRNA as Minimal Residual Disease in Leukemia: Diagnostic and Prognostic Approach: A Review

“…Increased expression of miR-362-5p as oncomiR through GADD45a down regulation and decreased expression of miR-320a as tumour suppressor through PI3K/AKT and NF-kb pathway are involved in the migration and invasion pathway ( 43 ). In this way, increasing the expression of miR-320a by inhibiting the phosphorylation of mentioned pathways leads to weakening the oncogenic function of bcr/abl ( 44 ).…”

“…Meanwhile, increasing its expression in THP-1 human leukaemia monocytic cell line produces the opposite result. By targeting DAB2, miR-93 inhibits the PI3K/AKT signalling pathway and increasing DAB2 expression negatively affects the growth of THP-1 cells ( 44 ). miR-125a acts as a tumour suppressor in patients with leukaemia.…”