CIRCRNA CIRCEHBP1 REGULATES THE MATURATION OF MIR-129 TO INCREASE THE CHEMORESISTANCE OF CANCER CELLS TO ADRIAMYCIN IN ACUTE MYELOID LEUKAEMIA

Abstract

Background: MiR-129 promotes the chemosensitivity of cancer cells in many cancers. The role of miR-129 in acute myeloid leukaemia (AML) is unclear. We predicted that premature miR-129 might interact with circEHBP1, a well-characterized oncogene in bladder cancer. We then analyzed the interaction between circEHBP1 and miR-129 in AML. Methods: Expression of circEHBP1 and miR-129 in AML patients) was determined by RT-qPCR before and after treatment with adriamycin (ADR. Detection of circEHBP1 was performed with cellular fractionation assay in nuclear and cytoplasm samples of AML cells. The direct interaction between circEHBP1 and premature miR-129 was explored with an RNA-RNA pulldown assay. Finally, overexpression assays followed by RT-qPCRs were performed to analyze the role of circEHBP1 in the maturation of miR-129. Results: Compared to controls, AML patients exhibited increased expression of circEHBP1 and premature miR-129 but decreased mature miR-129. Altered gene expression was more obvious in ADR resistant group than in the sensitive group. CircEHBP1 was detected in both nuclear and cytoplasm and directly interacted with premature miR-129. Overexpression of circEHBP1 increased the level of premature miR-129 but decreased the level of mature miR-129. In AML cells, circEHBP1 suppressed ADR-induced cell apoptosis and suppressed the enhancing effects of miR-129 on cell apoptosis. More importantly, the role of circEHBP1 in regulating cell apoptosis is more obvious in ADR resistance cells. Conclusion: Therefore, circEHBP1 may suppress the maturation of miR-129 to increase the chemoresistance of cancer cells to ADR in AML.   Keywords: acute myeloid leukaemia, circEHBP1, miR-129, adriamycin