Abstract
Abstract
Chronic myeloid leukemia (CML) is a malignant tumor that affects the blood and bone marrow. Its characteristic is the production of a large number of immature white blood cells, which aggregate in the bone marrow and inhibit normal hematopoiesis in the bone marrow. To date, CML is mainly treated through the use of tyrosine kinase inhibitors and hematopoietic stem cell transplantation. However, some patients may experience resistance to tyrosine kinase inhibitors and rejection reactions after transplantation of hematopoietic stem cells. In previous experiments, we found that oleanolic acid (OA) promoted an increase in reactive oxygen species (ROS) in K562 cells, decreased mitochondrial membrane potential, and decreased cell proliferation ability. Flow cytometry and CCK8 experiments have shown that OA can lead to the occurrence of cell apoptosis in a dose-dependent manner. Through further experiments, we found that after OA treatment, STK4 expression was upregulated and miRNA-18a-5p expression was downregulated in K562 cells. Surprisingly, the addition of miRNA-18a-5p mimics inhibited the expression of STK4 in cells; after adding the miRNA inhibitor, the expression of STK4 increased. Further research has shown that after overexpression of STK4, compared with the control group, the mitochondrial membrane potential of cells decreases and the proliferation ability significantly decreases. After interfering with STK4 and undergoing OA treatment, compared with the OA group, the decrease in mitochondrial membrane potential in the interference + OA group was inhibited, and the cell proliferation ability returned to the level of the control group. OA can maintain low expression of STK4 in K562 cells by upregulating miR-18a, which directly targets the STK4 mRNA 3'UTR. Downregulation of miR-18a increases STK4 expression. Our research results confirm that OA can promote apoptosis in K562 cells by maintaining low expression of miR-18a and keeping STK4 in a high expression state.
Publisher
Research Square Platform LLC