Cell Death Dis:低氧通过HIF/HEY1/PINK1通路调节肝癌细胞的线粒体活性

2020-01-12 QQY MedSci原创

缺氧在癌症中很常见。缺氧,由于缺乏氧气(O2)作为电子受体,导致通过线粒体电子传输链的电子转移效率低下,导致活性氧(ROS)积累,从而可能造成不可逆的细胞损伤。通过可引发各种分子事件的缺氧诱导因子1(HIF-1),细胞能够克服低氧。有关由HIF-1调控的新分子机制的知识对于针对缺氧肿瘤的新治疗干预非常重要。研究人员通过肝细胞癌(HCC)模型,发现HIF-1和Notch信号通路通过交叉作用来控制癌细

缺氧在癌症中很常见。缺氧,由于缺乏氧气(O2)作为电子受体,导致通过线粒体电子传输链的电子转移效率低下,导致活性氧(ROS)积累,从而可能造成不可逆的细胞损伤。通过可引发各种分子事件的缺氧诱导因子1(HIF-1),细胞能够克服低氧。有关由HIF-1调控的新分子机制的知识对于针对缺氧肿瘤的新治疗干预非常重要。

研究人员通过肝细胞癌(HCC)模型,发现HIF-1和Notch信号通路通过交叉作用来控制癌细胞的线粒体生物发生,以维持氧化还原(REDOX)平衡。通过转录组测序研究人员发现,在HCC细胞系中,NOTCH通路中的转录抑制因子HEY1始终受缺氧诱导。

此外,研究人员通过染色质免疫沉淀(ChIP)和荧光素酶报告基因分析发现了HEY1的一个强缺氧反应元件(HRE)。进一步研究明确,PINK1(线粒体生物发生必不可少的基因)是HEY1的新型转录靶点。敲低HEY1的HCC细胞会重新表达PINK1。

在人类HCC样本中,HEY1和PINK1表达呈负相关。在人类HCC中,检测到HEY1过表达和PINK1低表达,均与临床预后不良相关。在功能上,研究人员发现HEY1的过表达或敲低PINK1可持续减少线粒体嵴和线粒体质量,降低氧化应激水平,同时加速HCC的生长。

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    2020-04-01 维他命
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1976377, encodeId=5a4219e6377ad, 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=34, 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 Oct 30 23:13:00 CST 2020, time=2020-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961833, encodeId=d183196183309, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Apr 01 07:13:00 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013151, encodeId=5bed201315142, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Jun 17 01:13:00 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1977401, encodeId=6f0719e74019c, content=<a href='/topic/show?id=43d214294b7' target=_blank style='color:#2F92EE;'>#PINK1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14294, encryptionId=43d214294b7, topicName=PINK1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2978132, createdName=minzju5052, createdTime=Thu Sep 17 00:13:00 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871542, encodeId=68f318e1542f9, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Apr 24 16:13:00 CST 2020, time=2020-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252667, encodeId=759b125266e71, 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=26, 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=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531513, encodeId=411a1531513a7, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556044, encodeId=b56e155604429, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040257, encodeId=1954104025e37, content=肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=留走人康, createdTime=Mon Jan 13 00:13:00 CST 2020, time=2020-01-13, status=1, ipAttribution=)]
    2020-09-17 minzju5052
  5. [GetPortalCommentsPageByObjectIdResponse(id=1976377, encodeId=5a4219e6377ad, 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=34, 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 Oct 30 23:13:00 CST 2020, time=2020-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961833, encodeId=d183196183309, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Apr 01 07:13:00 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013151, encodeId=5bed201315142, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Jun 17 01:13:00 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1977401, encodeId=6f0719e74019c, content=<a href='/topic/show?id=43d214294b7' target=_blank style='color:#2F92EE;'>#PINK1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14294, encryptionId=43d214294b7, topicName=PINK1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2978132, createdName=minzju5052, createdTime=Thu Sep 17 00:13:00 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871542, encodeId=68f318e1542f9, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Apr 24 16:13:00 CST 2020, time=2020-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252667, encodeId=759b125266e71, 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=26, 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=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531513, encodeId=411a1531513a7, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556044, encodeId=b56e155604429, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040257, encodeId=1954104025e37, content=肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=留走人康, createdTime=Mon Jan 13 00:13:00 CST 2020, time=2020-01-13, status=1, ipAttribution=)]
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    2020-01-14 yxch36
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    2020-01-14 cy0328
  8. [GetPortalCommentsPageByObjectIdResponse(id=1976377, encodeId=5a4219e6377ad, 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=34, 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 Oct 30 23:13:00 CST 2020, time=2020-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961833, encodeId=d183196183309, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Apr 01 07:13:00 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013151, encodeId=5bed201315142, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Jun 17 01:13:00 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1977401, encodeId=6f0719e74019c, content=<a href='/topic/show?id=43d214294b7' target=_blank style='color:#2F92EE;'>#PINK1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14294, encryptionId=43d214294b7, topicName=PINK1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2978132, createdName=minzju5052, createdTime=Thu Sep 17 00:13:00 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871542, encodeId=68f318e1542f9, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Apr 24 16:13:00 CST 2020, time=2020-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252667, encodeId=759b125266e71, 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=26, 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=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531513, encodeId=411a1531513a7, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556044, encodeId=b56e155604429, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Tue Jan 14 12:13:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040257, encodeId=1954104025e37, content=肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=留走人康, createdTime=Mon Jan 13 00:13:00 CST 2020, time=2020-01-13, status=1, ipAttribution=)]
    2020-01-14 wrj0126
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    2020-01-13 留走人康

    肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负

    0

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多能调节通路的活化是实体肿瘤进展中的重要过程,目前研究表明缺氧的微环境可以增强一些细胞的干细胞特征。癌症干细胞(CSCs)/肿瘤起始细胞(TICs)可以增加侵袭、转移和耐药性。此前有研究报道了神经胶质瘤的全球低甲基化和位点特异性异常甲基化以及其他表观遗传修饰,它们是胶质瘤进展期间基因组不稳定性的重要参与因素。近期,一项发表在杂志Stem cells上的研究证明了缺氧介导的表观遗传修饰在调节神经胶质

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由此可见,在存在高血管密度的情况下,缺氧ECs的不良结局明显可见,这表明血管生成在缺氧EC的转移过程中具有重要作用。这可能需要对这些患者进行有差别的辅助治疗。

Radiology:氧增强MRI肾癌低氧图的价值

本研究旨在验证T1加权氧增强(OE)MRI评价肿瘤低氧耗指标,评价该技术应用于临床的可能性,将结果发表在radiology上。

Tissue Cell:低氧张力调节小鼠胚胎干细胞的成骨分化

本研究检测了低氧压力对三维培养系统中胚胎干细胞(ESCs)成骨分化的影响。首次证实低氧条件下低氧相关蛋白低氧诱导因子-1α和血管内皮生长因子的表达升高。随后通过测量碱性磷酸酶活性,细胞内钙水平,基质矿化和成骨标志物Runt相关转录因子2和osterix的蛋白质水平来评估低氧ESCs与成骨或无骨生长因子培养基的成骨分化。随后通过测量碱性磷酸酶活性,细胞内钙水平,基质矿化和成骨标志物Runt相关转录因