title: Downregulation of MicroRNA-152 contributes to high expression of DKK1 in multiple myeloma.
abstract: Multiple myeloma (MM) induced bone lesion is one of the most crippling characteristics, and the MM secreted Dickkopf-1 (DKK1) has been reported to play important role in this pathologic process. However, the underlying regulation mechanisms involved in DKK1 expression are still unclear. In this study, we validated the expression patterns of microRNA (miR) 15a, 34a, 152, and 223 in MM cells and identified that miR-152 was significantly downregulated in the MM group compared with the non-MM group, and that miR-152 level was negatively correlated with the expression of DKK1 in the MM cells. Mechanistic studies showed that manipulating miR-152 artificially in MM cells led to changes in DKK-1 expression, and miR-152 blocked DKK1 transcriptional activity by binding to the 3'UTR of DKK1 mRNA. Importantly, we revealed that MM cells stably expressing miR-152 improved the chemotherapy sensitivity, and counteracted the bone disruption in an intrabone-MM mouse model. Our study contributes better understanding of the regulation mechanism of DKK-1 in MM, and opens up the potential for developing newer therapeutic strategies in the MM treatment.
authors.affiliation: a Department of Clinical Laboratory ; Affiliated Yongchuan Hospital of Chongqing Medical University ; Chongqing , PR China.|d These authors contributed equally to this study.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: b Department of Neurology ; People's Hospital of Bishan District ; Bishan , Chongqing , PR China.|d These authors contributed equally to this study.
authors.forename: Bingda
authors.initials: B
authors.lastname: Chen
authors.affiliation: c Department of Hematopathology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Suraj K
authors.initials: SK
authors.lastname: George
authors.affiliation: a Department of Clinical Laboratory ; Affiliated Yongchuan Hospital of Chongqing Medical University ; Chongqing , PR China.
authors.forename: Beizhong
authors.initials: B
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008558:Melphalan / Q000494:pharmacology; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C550856:MIRN152 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008558:Melphalan
keywords: bone disruption; dickkopf homolog 1; microRNA152; multiple myeloma