title: Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells through down regulating Mcl-1.
abstract: MicroRNAs (miRNAs) are small, noncoding ribonucleic acids (ncRNAs), which regulate gene expression by targeting mRNAs for translational repression and degradation. Several lines of evidences have indicated that miRNAs act as tumor suppressors and oncogenes. However, the role of miRNAs in pathogenesis of multiple myeloma (MM) remains unclear. In this study, we examined the profile of miRNA expression of primary MM cells, using miRNA microarray and quantitative real-time polymerase chain reaction (qPCR) techniques. These results showed that in the bone marrow specimens analyzed, miRNA-29b was significantly downregulated. Similar results were also observed in human myeloma cell lines (HMCLs). Adenovirus-mediated overexpression of miR-29b induced apoptosis and elevated caspase-3 activation in HMCLs. Using a bioinformatics approach, we found a perfect complementarity between miRNA-29b and the 3'UTR of myeloid-cell-leukemia 1(Mcl-1). It is further confirmed that miRNA-29b downregulated the level of Mcl-1 without effect on the mRNA level using both qRT-PCR assays and Western blot analyses. Moreover, we observed that enforced miR-29b expression by using a retarget miRNA-29b expression vector (Ad5F11p-miR-29b) could induce apoptosis and elevate caspase-3 activation in HMCLs. Our results also indicated that miRNA-29b-induced apoptosis acted antagonistically with IL-6 in HMCLs. These findings suggest that miRNA-29b may play an important role in MM as a tumor suppressor.
authors.affiliation: Department of Haematology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Yi-Kun
authors.initials: YK
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Leng
authors.forename: Ze-Liang
authors.initials: ZL
authors.lastname: Li
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Yang
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Xiao
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Li
authors.forename: Xie-Qun
authors.initials: XQ
authors.lastname: Chen
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3