In SilicoStudy of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia

Abstract

Background: Chronic myeloid leukemia (CML) is associated with BCR-ABL1 gene that plays a central role in the pathogenesis of CML. Thus, it is crucial to supress the expression of BCR-ABL1 in the treatment of CML. MiRNA is known to be a gene expression regulator, thus it is a good candidate for molecularly targeted therapy for CML. Objective: This study aims to identify the miRNAs from edible plants that targeted the 3’ untranslated region (3’UTR) of BCR-ABL1. Method: In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were utilised to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. MiRBase database was used to validate the species of plants expressing the miRNAs. RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction respectively. Results: In silico analyses reveal cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b are having binding conformity with strong molecular interaction toward 3’UTR region of BCR-ABL1. However only cpa-miR-8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. Conclusion: It is predicted that these miRNAs post-transcriptionally inhibit BCR-ABL1 gene via cleavage and thus, they could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out in order to determine the ability of these miRNAs as a targeted therapy for CML.

Potential treatment for chronic myeloid leukemia using microRNA: in silico comparison between plants and human microRNAs in targeting BCR-ABL1 gene

“…b The first neighbors of selected nodes (ABL1) outgoing module in the network, including 19 nodes and 39 edges; the module function is closely related to the hemopoiesis, regulation of apoptotic process, regulation of cell population proliferation, and regulation of MAPK cascade Table 2 The first neighbors of selected nodes (ABL1) of osa-miR1858a, osa-miR1858b, and hsa-miR891a-3p target genes, pathways, and Gene Ontology analyzing complementary matching between sRNA and target mRNA sequences. It employed a predefined grading schema that evaluated the target site accessibility between miRNA and mRNA [27]. The analysis was continued by exporting miRNA sequences into another platform including RNA22 and Target Rank for further validation.…”