| Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen. | |
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MedLine Citation:
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PMID: 21460851 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit (hTERT) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen (ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G(0)-G(1) phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST-PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene in human tumorigenesis.Oncogene advance online publication, 4 April 2011; doi:10.1038/onc.2011.103. |
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Authors:
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Q Wang; D-C Li; Z-F Li; C-X Liu; Y-M Xiao; B Zhang; X-D Li; J Zhao; L-P Chen; X-M Xing; S-F Tang; Y-C Lin; Y-D Lai; P Yang; J-L Zeng; Q Xiao; X-W Zeng; Z-N Lin; Z-X Zhuang; S-M Zhuang; W Chen |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-04 |
Journal Detail:
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Title: Oncogene Volume: - ISSN: 1476-5594 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Toxicology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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