title: miR-17-92 cluster microRNAs confers tumorigenicity in multiple myeloma.
abstract: miRNAs play important roles in the regulation of cell proliferation, differentiation and apoptosis. The deregulation of miRNAs expression contributes to tumorigenesis by modulating oncogenic and tumor suppressor signaling pathways. Oncogenic transcription factor Myc can control expression of a large set of microRNAs (miRNAs). Previous studies have shown that the expression of miR-17-92 cluster, a polycistron encoding six microRNAs (miRNA), has close relationship with the expression of Myc. In current study, silencing Myc in multiple myeloma (MM)cells induced cell death and growth inhibition, and downregulated expression of miR-17-92 cluster. Overexpression of miR-17 or miR-18 could partly abrogated Myc-knockdown-induced MM cell apoptosis. One of the mechanism of Myc inhibiting MM cell apoptosis is through Myc activates miR-17-92 cluster and subsequently down-modulates proapoptotic protein Bim. Although miR-17-92 cluster are located at 13q31.3, the expression of miR-18, miR-19 and miR-20 (especially miR-19) in patients with del(13q14) was higher than those without del(13q14). Patients with miR-17, miR-20 and miR-92 high-expression had shorter PFS compared to those with miR-17, miR-20 and miR-92 low-expression. These results suggest the Myc-inducible miR-17-92 cluster miRNAs contribute to tumorigenesis and poor prognosis in multiple myeloma.
authors.affiliation: Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, China. Chenljb@126.com
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.forename: Chunming
authors.initials: C
authors.lastname: Li
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qu
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Chun
authors.initials: C
authors.lastname: Qiao
authors.forename: Jiaren
authors.initials: J
authors.lastname: Xu
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D005810:Multigene Family; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics
chemical_list: C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc