Cell Death Dis:TNFAIP8调节细胞自噬、脂肪变性并促进肝癌细胞增殖

2020-03-21 MedSci原创 MedSci原创

TNFAIP8(肿瘤坏死因子α诱导蛋白8)是TNFAIP8/TIPE蛋白家族的成员,该家族还包括TIPE1、TIPE2和TIPE3。TNFAIP8的表达与各种类型的肿瘤发生发展息息相关,其

TNFAIP8(肿瘤坏死因子α诱导蛋白8)是TNFAIP8/TIPE蛋白家族的成员,该家族还包括TIPE1、TIPE2和TIPE3。TNFAIP8的表达与各种类型的肿瘤发生发展息息相关,其影响肿瘤细胞的存活率及耐药性,但目前尚不清楚TNFAIP8发挥作用的详细机制。

该研究揭示了TNFAIP8在肝细胞癌(HCC)发生早期事件中的作用。HCC细胞中TNFAIP8表达水平的升高能够通过阻断细胞凋亡来提高细胞的存活率,从而使得HCC细胞对抗癌药物索拉非尼(sorafenib)及瑞格菲尼(regorafenib)具有更高的抵抗力。
 
TNFAIP8还可以诱导肝癌细胞自噬反应及脂肪变性。此外,TNFAIP8可以阻断AKT/mTOR信号转导通路,并能够于与ATG3-ATG7蛋白直接相互作用。TNFAIP8能够结合脂肪酸并调节脂质/脂肪酸代谢酶的表达水平。
 
对小鼠进行长期的酒精喂养会增加其肝脏中TNFAIP8表达、细胞自噬及脂肪变性的水平,但在高脂饮食的肥胖小鼠中并没有此现象。
 
同理,TNFAIP8的较高表达水平与有饮酒史的人类患者的脂肪肝相关,而与无饮酒史的肥胖患者无关。
 
以上研究结果表明,TNFAIP8在调节肿瘤抗药性、细胞自噬及肝脂肪变性等一系列肝细胞癌发生发展过程的关键早期事件中具有新的作用。

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    2020-08-01 docwu2019
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createdName=yilong5287542, createdTime=Fri Dec 11 02:22:02 CST 2020, time=2020-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961921, encodeId=19a91961921b0, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Sat Aug 01 05:22:02 CST 2020, time=2020-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1701039, encodeId=6def1e0103937, content=<a href='/topic/show?id=7113e15237a' target=_blank style='color:#2F92EE;'>#癌细胞增殖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71523, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401762, encodeId=45611401e62da, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Mar 23 11:22:02 CST 2020, time=2020-03-23, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=2013238, encodeId=f74e2013238d6, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Jul 16 16:22:02 CST 2020, time=2020-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1976378, encodeId=a6f519e637815, content=<a href='/topic/show?id=0ae08128e66' target=_blank style='color:#2F92EE;'>#肝癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81287, encryptionId=0ae08128e66, topicName=肝癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Fri Dec 11 02:22:02 CST 2020, time=2020-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961921, encodeId=19a91961921b0, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Sat Aug 01 05:22:02 CST 2020, time=2020-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1701039, encodeId=6def1e0103937, content=<a href='/topic/show?id=7113e15237a' target=_blank style='color:#2F92EE;'>#癌细胞增殖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71523, 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channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Oct 25 01:22:02 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948790, encodeId=5fb31948e905d, content=<a href='/topic/show?id=0602843360f' target=_blank style='color:#2F92EE;'>#脂肪变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84336, encryptionId=0602843360f, topicName=脂肪变性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Wed Dec 02 13:22:02 CST 2020, time=2020-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252680, encodeId=7dc51252680d5, content=<a href='/topic/show?id=3efee1519b2' target=_blank style='color:#2F92EE;'>#癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71519, encryptionId=3efee1519b2, topicName=癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cea26, createdName=yxch36, createdTime=Mon Mar 23 11:22:02 CST 2020, time=2020-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1299347, encodeId=a1c5129934eb3, content=<a href='/topic/show?id=1dd5e8010f5' target=_blank style='color:#2F92EE;'>#细胞自噬#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78010, encryptionId=1dd5e8010f5, topicName=细胞自噬)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Mon Mar 23 11:22:02 CST 2020, time=2020-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401762, encodeId=45611401e62da, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Mar 23 11:22:02 CST 2020, time=2020-03-23, status=1, ipAttribution=)]
    2020-11-28 fyxzlh
  6. [GetPortalCommentsPageByObjectIdResponse(id=2013238, encodeId=f74e2013238d6, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Jul 16 16:22:02 CST 2020, time=2020-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1976378, encodeId=a6f519e637815, content=<a href='/topic/show?id=0ae08128e66' target=_blank style='color:#2F92EE;'>#肝癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81287, encryptionId=0ae08128e66, topicName=肝癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401762, encodeId=45611401e62da, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Mar 23 11:22:02 CST 2020, time=2020-03-23, status=1, ipAttribution=)]
  7. 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  8. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401762, encodeId=45611401e62da, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Mar 23 11:22:02 CST 2020, time=2020-03-23, status=1, ipAttribution=)]
    2020-03-23 yxch36
  9. 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    2020-03-23 snowpeakxu

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Lancet oncol:PD-1抑制剂Camrelizumab治疗晚期肝癌患者的疗效和安全性

阻断PD-1与其配体的相互作用是治疗晚期肝癌的一种有希望的治疗策略。本研究旨在评估抗PD-1抑制剂camrelizumab在既往治疗过的晚期肝癌患者中的抗肿瘤活性和安全性。本研究是一个在中国的13个研究中心开展的多中心的开放性的平行组的随机化2期试验,招募年满18岁的病理确诊的、既往系统治疗后进展的或不能耐受的晚期肝癌患者。将受试患者随机(1:1)分至两组,分别2周或3周接受一次camrelizu

NEJM:5万人研究表明,“神药”阿司匹林或能预防肝癌

自1899年诞生以来,阿司匹林已经被研究者们用于多种疾病的治疗。从最初的镇痛解热,到抗血小板聚集,再到糖尿病、阿兹海默症治疗,都有它的身影。最近,顶级期刊《The New England Journa

NEJM:降低肝癌风险31%!“神药”阿司匹林再发威!

记得当初上药化课时,老师曾讲到阿司匹林,如果放到现在的研发流程里,可能前几轮就被筛掉了,因为它的作用实在是太多了。

Lancet Gastroen Hepatol:131I-西妥昔单抗辅助治疗改善肝癌切除患者预后

肝切除术后有效辅助治疗是肝细胞癌(HCC)是一个重要的研究领域。放射性碘( 131I)标记的西妥昔单抗针对HCC高表达的CD147 (又名 basigin 或 HAb18G)抗原的放射性单克隆抗体。近

Hepatol Int:乙型肝炎治疗患者肝癌发生风险:替诺福韦低于恩替卡韦

富马酸替诺福韦(TDF)在降低乙型肝炎患者肝细胞癌发生风险上是否优于恩替卡韦(ETV)目前仍存在争议。本研究拟从临床医学和方法学两方面的角度,通过荟萃分析来探讨这一问题。

Dig Liver Dis:高体重指数和饮酒对肝癌相关死亡率影响

目前已知高体重指数(BMI)和饮酒是肝癌的明确危险因素。本项研究的目的是在全球和国家层面描述高BMI和酒精摄入对肝癌相关死亡的影响。