...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis
【24h】

Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis

机译：miR-21等位基因的缺失可提高其靶基因的表达并减少肿瘤发生

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies. To determine whether miR-21 promotes tumor development in vivo, we knocked out the miR-21 allele in mice. In response to the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate mouse skin carcinogenesis protocol, miR-21-nu mice showed a significant reduction in papilloma formation compared with wild-type mice. We revealed that cellular apoptosis was elevated and cell proliferation was decreased in mice deficient of miR-21 compared to wild-type animals. In addition, we found that a large number of validated or predicted miR-21 target genes were up-regulated in miR-27-null keratinocytes, which are precursor cells to skin papillomas. Specifically, up-regulation of Spryi. Pten, and Pdcd4 when miR-21 was ablated coincided with reduced phosphor-ylation of ERK, AKT, and JNK, three major downstream effectors of Ras activation that plays a predominant role in DMBA-initiated skin carcinogenesis. These results provide in vivo evidence that miR-21 exerts its oncogenic function through negatively regulating its target genes.
机译：MicroRNA 21（miR-21）在所有类型的癌症和各种类型的血液系统恶性肿瘤中均过表达。为了确定miR-21是否在体内促进肿瘤发展，我们敲除了小鼠中的miR-21等位基因。响应7,12-二甲基苯并[a]蒽（DMBA）/ 12-O-十四烷酰佛波醇13-乙酸盐小鼠皮肤致癌方案，与野生型小鼠相比，miR-21-nu小鼠乳头瘤的形成明显减少。我们发现与野生型动物相比，miR-21缺陷型小鼠的细胞凋亡增加，细胞增殖减少。此外，我们发现在miR-27-null角质形成细胞（皮肤乳头状瘤的前体细胞）中，大量经过验证或预测的miR-21靶基因被上调。具体来说，上调Spryi。消除miR-21时的Pten和Pdcd4与ERK，AKT和JNK的磷酸化程度降低有关，这是Ras激活的三个主要下游效应子，在DMBA启动的皮肤癌变过程中起主要作用。这些结果提供了体内证据，证明miR-21通过负调控其靶基因发挥其致癌功能。

著录项

  • 来源
  • 作者

    Xiaodong Ma; Munish Kumar; Saibyasachi N. Choudhury; Lindsey E. Becker Buscaglia; Juanita R. Barker; Keerthy Kanakamedala; Mo-Fang Liu; Yong Li;

  • 作者单位

    Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY, 40202;

    Department of Biotechnology, Assam University (Central University), Silchar, Assam-788 011, India;

    rnDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY, 40202;

    Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY, 40202;

    Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY, 40202;

    Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY, 40202;

    rnState Key Laboratory of Molecular Biology,Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;

    rnDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY, 40202;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    microRNA; chemical-induced carcinogenesis; ras effector pathways;

    机译：微小RNA;化学诱导的致癌作用;ras效应子途径;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号