Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics
Xiong, Qian2; Zhong, Qiu3; Zhang, Jia1,2; Yang, Mingkun2; Li, Chongyang2; Zheng, Peng2; Bi, Li-Jun1; Ge, Feng2
2012-04-01
Source PublicationJOURNAL OF PROTEOME RESEARCH
ISSN1535-3893
Volume11Issue:4Pages:2078-2090
AbstractSubstantial evidence indicates that microRNA-21 (miR-21) is a key oncomiR in carcinogenesis and is significantly elevated in multiple myeloma (MM). In this study, we explored the role of miR-21 in human MM cells and searched for miR-21 targets. By knocking down the expression of endogenous miR-21 in U266 myeloma cells, we observed reduced growth, an arrested cell cycle, and increased apoptosis. To further understand its molecular mechanism in the pathogenesis of MM, we employed a SILAC (stable isotope labeling by amino acids in cell culture)-based quantitative proteomic strategy to systematically identify potential targets of miR-21. In total, we found that the expression of 178 proteins was up-regulated significantly by miR-21 inhibition, implying that they could be potential targets of miR-21. Among these, the protein inhibitor of activated STAT3 (PIAS3) was confirmed as a direct miR-21 target by Western blotting and reporter gene assays. We further demonstrated that miR-21 enhances the STAT3-dependent signal pathway by inhibiting the function of PIAS3 and that down-regulation of PIAS3 contributes to the oncogenic function of miR-21. This elucidation of the role of PIAS3 in the miR-21-STAT3 positive regulatory loop not only may shed light on the molecular basis of the biological effects of miR-21 observed in MM cells but also has direct implications for the development of novel anti-MM therapeutic strategies.
SubtypeArticle
KeywordMicrorna-21 (Mir-21) Multiple Myeloma (Mm) Stable Isotope LabelIng By AmIno Acids In Cell Culture (Silac) Signal Transducer And Activator Of Transcription 3 (Stat3) Protein Inhibitor Of Activated Stat3 (Pias3)
DOI10.1021/pr201079y
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS KeywordHUMAN GLIOBLASTOMA CELLS ; MICRORNA EXPRESSION ; GENE-EXPRESSION ; STAT3 INHIBITOR ; DOWN-REGULATION ; TUMOR-GROWTH ; PIAS3 ; ACTIVATION ; CANCER ; TRANSCRIPTION
WOS IDWOS:000302388100006
Citation statistics
Cited Times:47[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/27124
Collection藻类生物学及应用研究中心_水生生物分子与细胞生物学研究中心
Affiliation1.Chinese Acad Sci, Key Lab Noncoding RNA, Inst Biophys, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China
3.AntiTB Res Inst Guangdong Prov, IBPARI Joint Ctr Res TB, Guangzhou 510630, Guangdong, Peoples R China
Recommended Citation
GB/T 7714
Xiong, Qian,Zhong, Qiu,Zhang, Jia,et al. Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics[J]. JOURNAL OF PROTEOME RESEARCH,2012,11(4):2078-2090.
APA Xiong, Qian.,Zhong, Qiu.,Zhang, Jia.,Yang, Mingkun.,Li, Chongyang.,...&Ge, Feng.(2012).Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics.JOURNAL OF PROTEOME RESEARCH,11(4),2078-2090.
MLA Xiong, Qian,et al."Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics".JOURNAL OF PROTEOME RESEARCH 11.4(2012):2078-2090.
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