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Oncotarget：Aurora A激酶通过调节DNA修复与卵巢癌治疗相关

2017-07-19 Emma MedSci原创

AuroraA激酶卵巢癌DNA修复PARP
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卵巢癌发病隐匿，发现时往往已是疾病的晚期。手术治疗难以达到满意的疗效，化疗一般疗程长，副反应重，患者很难承受，且容易出现耐药。Aurora A激酶（AURKA）是极光激酶家族成员之一，为蛋白质丝氨酸/苏氨酸激酶，其通过调节有丝分裂和染色体不稳定性在卵巢癌的发展过程中起重要作用。PARP是细胞凋亡核心成员半胱天冬酶(caspase)的切割底物，它在DNA损伤修复与细胞凋亡中发挥着重要作用。

卵巢癌发病隐匿，发现时往往已是疾病的晚期。手术治疗难以达到满意的疗效，化疗一般疗程长，副反应重，患者很难承受，且容易出现耐药。Aurora A激酶（AURKA）是极光激酶家族成员之一，为蛋白质丝氨酸/苏氨酸激酶，其通过调节有丝分裂和染色体不稳定性在卵巢癌的发展过程中起重要作用。PARP是细胞凋亡核心成员半胱天冬酶(caspase)的切割底物，它在DNA损伤修复与细胞凋亡中发挥着重要作用。

发表于Oncotarget的一篇文章中，研究人员探究了AURKA在调节卵巢癌细胞DNA损伤反应和DNA修复中的作用。结果显示，AURKA能够调节PARP的表达和活性，研究人员还发现AURKA的一种新的调控DNA修复中非有丝分裂的功能，这为卵巢癌的治疗提供新靶点和新策略。

其中，使用小分子抑制剂alisertib特异性抑制AURKA活性，能够引起DNA-PKcs（双链断裂DSB修复所需的催化亚单位）活性升高，刺激非同源末端连接（NHEJ）修复途径，并降低DNA修复所必需的PARP和BRCA1/2的表达。体内研究结果与体外研究结果一致，alisertib处理增加了磷酸化的DNA-PKcs（pDNA-PKcsT2609），降低了PARP水平。

原始出处：
doi: 10.18632/oncotarget.18970.

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    2017-11-07 闆锋旦

    #target#

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    2018-01-03 sjq027

    #Aurora#

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    2017-07-23 Jackie Li

    学习

    0

  4. 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time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-21 Jackie Li

    学习

    0

  5. 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time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-20 虈亣靌

    学习了谢谢分享

    0

  6. 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time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-20 redcrab

    #激酶#

    0

  7. 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encodeId=284e224243ea, content=学习了，谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Thu Jul 20 12:27:26 CST 2017, time=2017-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223793, encodeId=d029223e9347, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Wed Jul 19 07:41:12 CST 2017, time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-20 jambiya

    #DNA修复#

    0

  8. 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time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-20 清风拂面

    学习了，谢谢分享

    0

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time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-19 榄枷檬

    谢谢分享

    0

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time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223785, encodeId=efe6223e853c, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Jul 19 07:38:34 CST 2017, time=2017-07-19, status=1, ipAttribution=)]
    2017-07-19 明月清辉

    谢谢分享，学习了

    0

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