Downregulation of miR-135a predicts poor prognosis in acute myeloid leukemia and regulates leukemia progression via modulating HOXA10 expression

Abstract

MicroRNA-135a (miR-135a) has been shown to exert important roles in various human cancer types, such as glioblastoma, thyroid carcinoma and renal carcinoma. However, the function of miR-135a in acute myeloid leukemia (AML) remains largely unknown. In the present study, it was demonstrated that miR-135a expression was significantly downregulated in AML cells compared with normal control cells. Furthermore, the downregulation of miR-135a in patients with AML predicted poor prognosis. Through functional experiments, overexpression of miR-135a was demonstrated to significantly inhibit the proliferation and cell cycle of AML cells, while it promoted cellular apoptosis. miR-135a directly targeted HOXA10 in AML cells. miR-135a overexpression significantly suppressed the mRNA and protein levels of HOXA10 in AML cells. Moreover, there was an inverse association between miR-135a expression and HOXA10 level in AML samples. Additionally, by ectopic expression of HOXA10, restoration of HOXA10 significantly abolished the effects of miR-135a overexpression on AML cell proliferation, cell cycle and apoptosis. In conclusion, the present study demonstrated that miR-135a serves as a tumor suppressor in AML by targeting HOXA10, and miR-135a may be a promising prognostic biomarker for AML patients.