MiRNA-149* promotes cell proliferation and suppresses apoptosis by mediating JunB in T-cell acute lymphoblastic leukemia. (February 2016)

• Record Type: Journal Article
• Authors: Fan, Sheng-jin; Li, Hui-bo; Cui, Gang; Kong, Xiao-lin; Sun, Li-li; Zhao, Yan-qiu; Li, Ying-hua; Zhou, Jin
• Is Part Of: Leukemia research. Volume 41(2016:Feb.)
• Page Start: 62
• Page End: 70
• Publication Date: 2016-02
• Subjects: miRNA-149* -- JunB -- T-ALL -- Proliferation -- Apoptosis; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2015.11.016
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: miRNA-149* was upregulated in T-ALL cells and T-ALL patients' bone marrow samples. JunB was a target of miR-149*, and miRNA-149* mimics downregulated JunB levels. miRNA-149* mimics promoted proliferation and reduced cell apoptosis in T-ALL cells. miRNA-149* mimics downregulated p21 and upregulated cyclinD1, 4EBP1, and p70s6k. miRNA-149* inhibitors exhibited opposite effects. Abstract: MicroRNA-149* (miRNA-149*) functions as an oncogenic regulator in human melanoma. However, the effect of miRNA-149* on T-cell acute lymphoblastic leukemia (T-ALL) is unclear. Here we aimed to analyze the effects of miRNA-149* on in vitro T-ALL cells and to uncover the target for miRNA-149* in these cells. The miRNA-149* level was determined in multiple cell lines and bone marrow cells derived from patients with T-ALL, B acute lymphoblastic leukemia (B-ALL), acute myelocytic leukemia (AML), and healthy donors. We found that miRNA-149* was highly expressed in T-ALL cell lines and T-ALL patients' bone marrow samples. JunB was identified as a direct target of miR-149*. miRNA-149* mimics downregulated JunB levels in Molt-4 and Jurkat cells, while miRNA-149* inhibitors dramatically upregulated JunB expression in these cells. miRNA-149* mimics promoted proliferation, decreased the proportion of cells in G1 phase, and reduced cell apoptosis in T-ALL cells, while miRNA-149* inhibitors prevented these effects. miRNA-149* mimics downregulated p21 and upregulated cyclinD1, 4EBP1, and p70s6k in Molt-4 and Jurkat cells. Again, inhibitors prevented these effects. Our findings demonstrate that miRNA-149* may serve as an oncogenic regulator in T-ALL by negatively regulating JunB .