title: Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin.
abstract: RNA-binding protein Musashi-2 (Msi2) is known to play a critical role in leukemogenesis and contributes to poor clinical prognosis in acute myeloid leukemia (AML). However, the effect of Msi2 silencing on treatment for AML still remains poorly understood. In this study, we used lentivirus-mediated RNA interference targeting Msi2 to investigate the resulting changes in cellular processes and the underlying mechanisms in AML cell lines as well as primary AML cells isolated from AML patients. We found that Msi2 was highly expressed in AML cells, and its depletion inhibited Ki-67 expression and resulted in decreased in vitro and in vivo proliferation. Msi2 silencing induced cell cycle arrest in G0/G1 phase, with decreased Cyclin D1 and increased p21 expression. Msi2 silencing induced apoptosis through down-regulation of Bcl-2 expression and up-regulation of Bax expression. Suppression of Akt, Erk1/2 and p38 phosphorylation also contributed to apoptosis mediated by Msi2 silencing. Finally, Msi2 silencing in AML cells also enhanced their chemosensitivity to daunorubicin. Conclusively, our data suggest that Msi2 is a promising target for gene therapy to optimize conventional chemotherapeutics in AML treatment.
authors: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors: Yixiang
authors: Y
authors: Han
authors: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors: Aifang
authors: A
authors: Ye
authors: Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, 200032, China.
authors: Yan
authors: Y
authors: Zhang
authors: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors: Zhimin
authors: Z
authors: Cai
authors: Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
authors: Lan
authors: L
authors: Sun
authors: Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
authors: Songfu
authors: S
authors: Jiang
authors: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors: Jianbo
authors: J
authors: Wu
authors: Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
authors: Kang
authors: K
authors: Yu
authors: Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
authors: Shenghui
authors: S
authors: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; C438151:MSI2 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D003630:Daunorubicin