ArticleCell journal2024
Bioinformatics-Guided Discovery of miRNAs Involved in Apoptosis Modulated by Parthenolide Combined with Vincristine in The NALM6 Cell Line.
Article in Cell journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors at 3 institutions in 2 countries.
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Abstract
objectiveAcute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the MATERIALS AND
methodsIn this experimental study, cell viability and metabolic activity were determined through MTT assay and PI staining. Flow cytometry was applied to evaluate the rate of apoptosis. The expression of miRNAs was assessed using real-time polymerase chain reaction. Bioinformatic analyses, including Cytoscape, RNAhybrid, and signaling pathway analysis were employed to investigate the association of miR-17-5p, miR-181b-5p and miR-125b- 5p with apoptosis. Further, molecular docking served to validate the modulation of these miRNAs by parthenolide and vincristine treatment.
resultsThe MTT assay indicated that 7.7 μM of parthenolide decreased the metabolic activity to 50% after 48 hours. PI staining analysis indicated that at concentrations below the half maximal inhibitory concentration, parthenolide caused 50% cell death. Flow cytometric analysis indicated that parthenolide (1.925 μM) in combination with vincristine (1.2 nM) induced apoptosis in 83.2% of the cells. Real-time quantitative reverse transcription polymerase chain reaction (qRTPCR) analysis showed significant changes in the expression levels of miR-17-5p, miR-125b-5p, and miR-181b-5p. Moreover, the combination therapy downregulated the expression of miRNAs significantly. This was consistent with our bioinformatic analysis demonstrating that the studied miRNAs are regulators of apoptosis. Finally, molecular docking validated the modulation of the miRNAs by parthenolide and vincristine.
conclusionParthenolide in combination with vincristine triggers apoptosis at a high rate in the NALM6 cell line. Moreover, this combination therapy can decrease the expression of miR-17-5p, miR-181b-5p, and miR-125b-5p.
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