International Journal of Hematology and Oncology 2024, Vol 34, Num 1 Page(s): 238-247
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


1Shiraz University of Medical Sciences, Hematology Research Center, Shiraz, IRAN
2Shiraz University of Medical Sciences, Transplant Research Center, Shiraz, IRAN

Keywords: MicroRNA; Acute myeloid leukemia (AML); locked nucleic acid (LNA)-anti-miRNA; Gene expression
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 c-Kit, 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.