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学科主题: 医学信息学
题名:
Sulindac inhibits tumor cell invasion by suppressing NF-kappa B-mediated transcription of microRNAs
作者: Li, X.1; Gao, L.1; Cui, Q.2; Gary, B. D.1; Dyess, D. L.3; Taylor, W.1; Shevde, L. A.1; Samant, R. S.1; Dean-Colomb, W.1; Piazza, G. A.1; Xi, Y.1
关键词: sulindac ; invasion ; microRNA ; NF-kappa B
刊名: ONCOGENE
发表日期: 2012-11-01
DOI: 10.1038/onc.2011.655
卷: 31, 期:48, 页:4979-4986
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]: COLON-CANCER CELLS ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; FAMILIAL ADENOMATOUS POLYPOSIS ; HUMAN BREAST-CANCER ; COLORECTAL-CANCER ; REDUCED EXPRESSION ; E-CADHERIN ; RT-PCR ; METASTASIS ; APOPTOSIS
英文摘要:

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely reported to display strong efficacy for cancer chemoprevention, although their mechanism of action is poorly understood. The most well-documented effects of NSAIDs include inhibition of tumor cell proliferation and induction of apoptosis, but their effect on tumor cell invasion has not been well studied. Here, we show that the NSAID, sulindac sulfide (SS) can potently inhibit the invasion of human MDA-MB-231 breast and HCT116 colon tumor cells in vitro at concentrations less than those required to inhibit tumor cell growth. To study the molecular basis for this activity, we investigated the involvement of microRNA (miRNA). A total of 132 miRNAs were found to be altered in response to SS treatment, including miR-10b, miR-17, miR-21 and miR-9, which have been previously implicated in tumor invasion and metastasis. We confirmed that these miRNA can stimulate tumor cell invasion and show that SS can attenuate their invasive effects by downregulating their expression. Employing luciferase and chromatin immunoprecipitation assays, NF-kappa B was found to bind the promoters of all four miRNAs to suppress their expression at the transcriptional level. We show that SS can inhibit the translocation of NF-kappa B to the nucleus by decreasing the phosphorylation of IKK beta and I kappa B. Analysis of the promoter sequences of the miRNAs suppressed by SS revealed that 81 of 115 sequences contained NF-kappa B-binding sites. These results show that SS can inhibit tumor cell invasion by suppressing NF-kappa B-mediated transcription of miRNAs. Oncogene (2012) 31, 4979-4986; doi:10.1038/onc.2011.655; published online 30 January 2012

语种: 英语
所属项目编号: R01CA148817
项目资助者: National Cancer Institute
WOS记录号: WOS:000311888600002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52057
Appears in Collections:基础医学院_医学信息学系_期刊论文

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作者单位: 1.Univ S Alabama, Dept Surg, Mobile, AL 36604 USA
2.Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA
3.Peking Univ, Hlth Sci Ctr, Dept Biomed Informat, Beijing 100871, Peoples R China

Recommended Citation:
Li, X.,Gao, L.,Cui, Q.,et al. Sulindac inhibits tumor cell invasion by suppressing NF-kappa B-mediated transcription of microRNAs[J]. ONCOGENE,2012,31(48):4979-4986.
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