title: 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.
authors.affiliation: Department of Laboratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan, Guangdong, P.R. China.
authors.forename: Jinbang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yun
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Youming
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xiao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051153:Wnt Proteins