title: miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9 pathway.
abstract: Wnt/β-catenin signaling underlies the pathogenesis of a broad range of human cancers, including the deadly plasma cell cancer multiple myeloma. In this study, we report that downregulation of the tumor suppressor microRNA miR-30-5p is a frequent pathogenetic event in multiple myeloma. Evidence was developed that miR-30-5p downregulation occurs as a result of interaction between multiple myeloma cells and bone marrow stromal cells, which in turn enhances expression of BCL9, a transcriptional coactivator of the Wnt signaling pathway known to promote multiple myeloma cell proliferation, survival, migration, drug resistance, and formation of multiple myeloma cancer stem cells. The potential for clinical translation of strategies to re-express miR-30-5p as a therapeutic approach was further encouraged by the capacity of miR-30c and miR-30 mix to reduce tumor burden and metastatic potential in vivo in three murine xenograft models of human multiple myeloma without adversely affecting associated bone disease. Together, our findings offer a preclinical rationale to explore miR-30-5p delivery as an effective therapeutic strategy to eradicate multiple myeloma cells in vivo.
authors.affiliation: Authors' Affiliations: Department of Medical Oncology; Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute; Harvard School of Public Health; Department of Pathology, Brigham & Women's Hospital; Department of Developmental Biology, Harvard School of Dental Medicine; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and Experimental Therapies, H. Lee Moffitt Cancer Center, Florida; and Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Jianhong
authors.initials: J
authors.lastname: Lin
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.forename: Xujun
authors.initials: X
authors.lastname: Wang
authors.forename: Daniel
authors.initials: D
authors.lastname: Brooks
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Zhang-Bo
authors.initials: ZB
authors.lastname: Chu
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.forename: Bryan
authors.initials: B
authors.lastname: Ciccarelli
authors.forename: Samir
authors.initials: S
authors.lastname: Admin
authors.forename: Jianguo
authors.initials: J
authors.lastname: Tao
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.forename: Steven
authors.initials: S
authors.lastname: Treon
authors.forename: Geraldine
authors.initials: G
authors.lastname: Pinkus
authors.forename: Winston Patrick
authors.initials: WP
authors.lastname: Kuo
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Mary
authors.initials: M
authors.lastname: Bouxsein
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anderson
authors.forename: Ruben
authors.initials: R
authors.lastname: Carrasco
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism; D034622:RNA Interference; D014157:Transcription Factors; D047368:Tumor Burden; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C111180:BCL9 protein, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D014157:Transcription Factors