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题名: Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics
作者: Xiong, Qian2; Zhong, Qiu3; Zhang, Jia1, 2; Yang, Mingkun2; Li, Chongyang2; Zheng, Peng2; Bi, Li-Jun1; Ge, Feng2
关键词: microRNA-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)
刊名: JOURNAL OF PROTEOME RESEARCH
发表日期: 2012-04-01
DOI: 10.1021/pr201079y
卷: 11, 期:4, 页:2078-2090
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Biochemical Research Methods
研究领域[WOS]: Biochemistry & Molecular Biology
英文摘要: Substantial 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.
关键词[WOS]: HUMAN GLIOBLASTOMA CELLS ; MICRORNA EXPRESSION ; GENE-EXPRESSION ; STAT3 INHIBITOR ; DOWN-REGULATION ; TUMOR-GROWTH ; PIAS3 ; ACTIVATION ; CANCER ; TRANSCRIPTION
语种: 英语
WOS记录号: WOS:000302388100006
ISSN号: 1535-3893
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内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/27124
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.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
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