Investigation of the effect of silencing of leukemia-associated miRNAs on expression levels of target genes in addition to prednisolone administration in childhood acute lymphoblastic leukemia cell lines.

Project no. 22334 · Status: Kapanmış · 2020

Summary

Approximately seventy-five percent of childhood leukemias are acute lymphoblastic leukemia (ALL) and its etiology is not exactly known. In current studies on leukemia, microRNA (miRNA), a current molecule that shows its effect through an epigenetic mechanism, draws attention. Post-transcriptional targeting of leukemia-related genes is an important anti-leukemic strategy. In this context, it was aimed to determine the expression levels of AICDA, MYO10, CBFB, PELI1, CD47, PODXL, CD69; RAB6A, CLDN1, RCOR1, CSF1R, TAB2, CTLA4, TNFRSF10A, FGF7, TRIP13, MSH6, and UBE2J1 genes.For this purpose, silencing of miR-146a, miR-155, and miR-181a was achieved by the specific anti-miRs to childhood B-ALL cell line SUP-B15 cells and human healthy B-lymphocyte cell line NCI-BL2171 cells. This procedure has been expanded to include combined application groups with the prednisolone that is conventionally used in leukemia. Changes in mRNA level of target genes resulting from silencing were determined by real-time qRT-PCR method and calculated by 2-∆∆Ct method.As a result, a significant decrease was determined in the expression level of the MYO10 gene, especially in the group in which four miRNAs were silenced and prednisolone was applied in combination, compared to the control.In conclusion, in this study, we aimed to elucidate the molecular mechanism of silencing miR-146a, miR-155, miR-181a, and let-7'e alone or together, and this application in combination with prednisolone used in conventional therapy. We suggest that MYO10 plays a critical role and that this gene may constitute a critical target in ALL.

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