MiR-181a-5p, an inducer of Wnt-signaling, facilitates cell proliferation in acute lymphoblastic leukemia.

Abstract

Uncontrolled Wnt signaling causes leukemia. Inactivation of Wnt antagonists could play an important role in leukemia progression by activating the Wnt/β-catenin pathway. Wnt inhibitory factor-1 (WIF1) is one of the important Wnt antagonists. Few miRNAs have been reported to directly target this gene in hematopoiesis. Here, we observed that miR-181a-5p expression was markedly overexpressed in several leukemia cell lines and acute lymphoblastic leukemia (ALL) samples compared with that noted in normal peripheral blood mononuclear cells. MTT assays, soft agar colony formation assays and flow cytometry analysis collectively showed that ectopic expression of miR-181a-5p induced ALL cell growth and proliferation. Furthermore, a mechanistic study disclosed that miR-181a-5p directly downregulated WIF1 expression by binding to its 3'-UTR, and further activated Wnt/β‑catenin signaling. These findings provide a novel mechanistic insight into the role of miR-181a-5p in ALL cell growth and proliferation and implicate miR-181a-5p as an attractive candidate for ALL therapy.