title: MiRNA-34a overexpression inhibits multiple myeloma cancer stem cell growth in mice by suppressing TGIF2.
abstract: Hematological malignancy originated from B-cell line, multiple myeloma (MM), is a kind of plasma cells in bone marrow hyperplasia and cause of osteoclast-mediated skeletal destruction disease. MiR-34a plays an important epigenetic regulating role in malignant tumors and presents a therapeutic potential. In this study, we investigated the effects of overexpression of miR-34a in MM cancer stem cells (CSCs) on tumor growth and bone lesions. Here we showed that miR-34a overexpression inhibited cell proliferation, colony formation, and increased CSC apoptosisin vitro. The apparent epigenetic modulation induced by miR-34a overexpression was found no only in MM RPMI8226 cells but also in CSC xenograft MM. Both bioinformatics prediction and dual-luciferase reporter assay showed that transforming growth interaction factor 2 (TGIF2) was sufficient to confer miR-34a regulation. The results of qRT-PCR and Western blot assays demonstrated that the expression of TGIF2 was significant decreased in tumor tissues from NOD/SCID mice injected with miR-34a-MM CSCs. We conclude that miR-34a overexpression in MM CSCs significantly suppressed the tumorigenicity and lytic bone lesions in mouse model by inducing apoptosis and inhibiting TGIF2 expression.
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast UniversityNanjing 210009, China; Changzhou Blood CenterChangzhou 213004, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University Nantong 226361, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Biological Science & Medical Engineering, Southeast University Nanjing 210096, China.
authors.forename: Shouhua
authors.initials: S
authors.lastname: Luo
authors.affiliation: School of Biological Science & Medical Engineering, Southeast University Nanjing 210096, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
keywords: Multiple myeloma; cancer stem cells; miR-34a; transforming growth interaction factor 2