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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a
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cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a

机译：cAMP反应元件结合蛋白通过调节致癌微RNA-23a的表达促进神经胶质瘤发生

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摘要

Gliomas are the most common and deadly type of primary brain tumor. In this study, we showed that cAMP response element-binding protein (CREB), a proto-oncogenic transcription factor that is overex-pressed in gliomas, can promote gliomagenesis by modulating the expression of oncogenic microRNA-23a (mir-23a). First, we found that CREB is highly expressed in glioma tissues and cell lines. CREB is also essential for glioma cell growth and cell survival in vitro and is critical for gliomagenesis in vivo. Second, microRNA microarray, ChlP-chip, ChlP-quantitative PCR, and luciferase reporter assays showed that CREB directly binds to the regulatory sequences of mir-23a and enhance the expression of mir-23a. Moreover, mir-23a was confirmed as a functional downstream target of CREB in glioma cell growth and cell survival. Finally, using computational prediction followed by experimental confirmation, we identified PTEN, which is frequently silenced in gliomas, as a downstream target of mir-23a. Taken together, we propose that CREB promotes gliomagenesis and acts as a modulator of oncogenic mir-23a, which represses the tumor suppressor PTEN.
机译：神经胶质瘤是最常见和致命的原发性脑肿瘤。在这项研究中，我们表明cAMP反应元件结合蛋白（CREB），是一种在胶质瘤中过表达的原癌基因转录因子，可以通过调节致癌性microRNA-23a（mir-23a）的表达来促进胶质瘤的发生。首先，我们发现CREB在神经胶质瘤组织和细胞系中高表达。 CREB对于神经胶质瘤细胞的生长和体外细胞存活也是必不可少的，并且对于体内神经胶质瘤的形成也至关重要。其次，microRNA微阵列，ChlP芯片，ChlP定量PCR和萤光素酶报告基因检测表明CREB直接与mir-23a的调控序列结合并增强mir-23a的表达。此外，mir-23a被确认为胶质瘤细胞生长和细胞存活中CREB的功能性下游目标。最后，使用计算预测和实验确认，我们确定了在胶质瘤中经常沉默的PTEN作为mir-23a的下游靶标。两者合计，我们建议CREB促进神经胶质瘤发生并充当致癌的mir-23a的调节剂，它抑制肿瘤抑制物PTEN。

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    Xiaochao Tan; Shan Wang; Liyuan Zhu; Chao Wu; Bin Yin; Jizong Zhao; Jiangang Yuan; Boqin Qiang; Xiaozhong Peng;

  • 作者单位

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China,Graduate School, Peking Union Medical College, Tsinghua University, Beijing 100005, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China,Graduate School, Peking Union Medical College, Tsinghua University, Beijing 100005, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China,Graduate School, Peking Union Medical College, Tsinghua University, Beijing 100005, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China,Graduate School, Peking Union Medical College, Tsinghua University, Beijing 100005, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China;

    Department of Neurosurgery, Beijing Tiantan Hospital, Beijing 100050, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China;

    State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China;

  • 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);
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