CircRNA CircEHBP1 Regulates the Maturation of MiR-129 to Increase the Chemoresistance of Cancer Cells to Adriamycin in Acute Myeloid Leukaemia

BACKGROUND: MicroRNA-129 (miR-129) is known to promote chemosensitivity of many types of cancer cells. However, 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, and analyzed the interaction between circEHBP1 and miR-129 in AML. METHODS: Expression of circEHBP1 and miR-129 in AML patients before and after adriamycin (ADR) treatment was determined by RT-qPCR. CircEHBP1 distribution in nuclear and cytoplasm fractions of AML cells was determined using a cellular fractionation assay. The direct interaction of circEHBP1 with premature miR-129 was explored with an RNA-RNA pull-down assay. Finally, the role of circEHBP1 in regulating miR-129 maturation was analyzed in overexpression cells by RT-qPCRs. RESULTS: Compared to the controls, AML patients exhibited increased circEHBP1 and premature miR-129 levels but decreased mature miR-129 levels. Altered gene expression was more obvious in ADR resistant group than in ADR sensitive group. CircEHBP1 was detected in both nuclear and cytoplasm fractions of AML cells and directly interacted with premature miR-129. CircEHBP1 overexpression increased premature miR-129 level but decreased mature miR-129 level. In AML cells, circEHBP1 suppressed ADR-induced cell apoptosis and attenuated the enhancing effects of miR-129 on cell apoptosis. More importantly, the role of circEHBP1 in regulating cell apoptosis was more obvious in ADR resistance cells. CONCLUSION: CircEHBP1 may suppress miR-129 maturation to increase the chemoresistance of cancer cells to ADR in AML.