Up-Regulation of the miR-92a and miR-181a in Patients with Acute Myeloid Leukemia and their Inhibition with Locked Nucleic acid (LNA)-antimiRNA; Introducing c-Kit as a New Target Gene

Özet

Dysregulated expression of various microRNAs (miRNAs) has been widely observed in hematopoietic malignancies like acute myeloid leukemia (AML). In this study, we evaluated the expression of the miR-92a and miR-181a in newly diagnosed AML patients compared to healthy controls. Also, we investigated for the first time the effect of blocking of the miR-92a and miR-181a on the expression of cKit, CEBPA and WT1 genes in HL-60 cell line. For evaluation of the relative gene expression, SYBR Green Real-Time PCR method was performed. The expression of miRNAs was inhibited by transfection of the HL-60 cell line with locked nucleic acid (LNA)-anti-miRNA. The viability of transfected cells was evaluated by MTT assay. Both miR-92a and miR-181a are highly overexpressed in AML patients compared to healthy controls. Also, miR-181a expression was associated with poor prognosis of AML patients. The blockage of the miR-92a and miR-181a remarkably reduces cell viability. In addition, inhibition of miR-92a with LNA-anti-miR-92a significantly decreased c-Kit level. Conversely, miR-181a blockage was associated with upregulated c-Kit expression. Taking together, miR-92a and miR-181a are dysregulated in AML patients and c-Kit gene might be a novel target for these miRNAs. Regarding the anti-proliferative effect of LNA-anti-miR-92a and LNA-anti-miR-181a, regulation of miR-92a and miR-181a expression might be a useful approach in line with conventional chemotherapy to limit blast cell survival and reduce leukemic cell proliferation.