Nat Commun:前列腺癌中组蛋白甲基转移酶DOT1L能够协调AR和MYC的稳定性

2020-09-02 AlexYang MedSci原创

组蛋白甲基转移酶DOT1L能够甲基化组蛋白H3上的赖氨酸79(K79),并与混合系白血病(MLL)融合白血病的发生有关;然而,DOT1L在前列腺癌(PCa)中的作用尚未确定。

组蛋白甲基转移酶DOT1L能够甲基化组蛋白H3上的赖氨酸79(K79),并与混合系白血病(MLL)融合白血病的发生有关;然而,DOT1L在前列腺癌(PCa)中的作用尚未确定。

最近,有研究人员研究表明,DOT1L在PCa中过表达并与不良结果有关。DOT1L的遗传和化学抑制能够选择性地损害雄激素受体(AR)阳性PCa细胞和类器官的生活力,其中包括了去势抗性和恩杂鲁胺抗性细胞。AR阳性细胞的敏感性是由AR和DOT1L结合的MYC基因中的远端K79甲基化标记增强子引起的,且在AR阴性细胞中不存在。DOT1L的抑制能够导致MYC表达减少,并上调MYC调控的E3泛素连接酶HECTD4和MYCBP2,从而促进AR和MYC的降解。这导致MYC以负前馈调节的方式进一步受到抑制。

DOT1L在前列腺癌中表达上调且其高表达与不良无疾病生存相关

最后,研究人员指出,DOT1L选择性地调节AR阳性前列腺癌细胞的致瘤性,是PCa的一个有希望的治疗靶点。

原始出处:

R. Vatapalli, V. Sagar, Y. Rodriguez et al. Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nat Commun. August 2020

 

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    2021-01-06 liye789132251
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    2021-05-13 liuli5079
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    2020-09-04 guihongzh
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    2020-09-04 xqptu
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    2020-09-03 ms3000000449926787

    学习了!

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1884615, encodeId=50db1884615f1, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Jan 06 00:56:07 CST 2021, time=2021-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087754, encodeId=1447208e7547f, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu May 13 20:56:07 CST 2021, time=2021-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1900537, encodeId=2c5e190053ead, content=<a href='/topic/show?id=0983e529745' target=_blank style='color:#2F92EE;'>#稳定性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75297, encryptionId=0983e529745, topicName=稳定性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e0a1165, createdName=jiangfeng5067, createdTime=Sat Nov 28 08:56:07 CST 2020, time=2020-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1934973, encodeId=7f5019349e342, content=<a href='/topic/show?id=195d69e935a' target=_blank style='color:#2F92EE;'>#甲基转移酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69793, encryptionId=195d69e935a, topicName=甲基转移酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1c2e485, createdName=yangfl06, createdTime=Thu Jun 03 12:56:07 CST 2021, time=2021-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1274837, encodeId=e44c12e48377c, content=<a href='/topic/show?id=1bbc12404ba' target=_blank style='color:#2F92EE;'>#MYC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12404, encryptionId=1bbc12404ba, topicName=MYC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Fri Sep 04 12:56:07 CST 2020, time=2020-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384704, encodeId=397a1384e04a2, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Fri Sep 04 12:56:07 CST 2020, time=2020-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882542, encodeId=0b8988254220, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Sep 03 20:31:59 CST 2020, time=2020-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040823, encodeId=ded3104082392, content=前列腺癌相关研究,学习了,谢谢梅斯, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Thu Sep 03 00:56:07 CST 2020, time=2020-09-03, status=1, ipAttribution=)]
    2020-09-03 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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