Cell Death Differ:外泌体miRNA miR-101-3p和miR-423-5p可抑制髓母细胞瘤的发生发展

2021-07-24 xiaozeng MedSci原创

髓母细胞瘤(MB)是儿童中最常见的一种恶性脑肿瘤。

髓母细胞瘤(MB)是儿童中最常见的一种恶性脑肿瘤。在当前标准的多模式治疗下,MB患者的5年总生存率约为60-70%,该治疗策略包括最大程度的安全的肿瘤切除、化疗以及放疗治疗。

然而幸存者在这些积极治疗后经常会遭受严重的长期后遗症,包括神经认知障碍、内分泌缺陷,甚至继发性肿瘤的发生。因此,迫切需要更有效的、毒性更低的疗法来改善MB患者的预后和生活质量。


外泌体是一种脂质双层封闭的囊泡,直径为30-150nm,由多种类型的细胞主动分泌。外泌体作为多种生物活性分子(包括蛋白质、脂质、mRNA 和miRNA)的载体,对于细胞通讯至关重要。外泌体除了参与正常的生理过程外,也具有重要的病理生理作用,包括在血管疾病、炎症反应、神经退行性疾病和肿瘤的发生发展中的作用。

既往研究显示,外泌体miRNA与多种肿瘤的发生发展息息相关。然而,其对MB发生发展的作用仍有待阐明。


研究人员首先通过miRNA测序分析外泌体miRNA的表达谱,以鉴定MB儿童和健康对照之间差异表达的miRNA。其次,对鉴定的miRNA及其预测靶标进行功能测定。

髓母细胞瘤患者外泌体miRNAs的差异表达

研究人员发现,相比于健康对照,从MB患者血浆中分离的外泌体中有35种miRNA的表达上调,另外5种表达下调。进一步的研究显示,在扩大的队列中,MB患者血浆外泌体中miR-101-3p和miR-423-5p的表达水平显著高于健康对照,且这些miRNA可通过外泌体递送至肿瘤细胞中。


体外功能研究显示,采用miR-101-3p和miR-423-5p的相应模拟物处理MB细胞可显著抑制肿瘤细胞的增殖、集落形成能力、迁移能力和侵袭能力,并促进细胞的凋亡。此外,miR-101-3p和miR-423-5p可通过直接靶向共同基因FOXP4来充当肿瘤抑制因子,FOXP4编码的转录因子在胚胎发育和肿瘤发生中起着重要作用。

相关研究示意图

此外,miR-101-3p还会靶向组蛋白甲基转移酶EZH2,以增强其肿瘤抑制作用。在MB的移植瘤裸鼠模型中,研究人员发现,miR-101-3p和miR-423-5p的过表达会抑制肿瘤的发生。


总而言之,该研究结果揭示了外泌体miRNA在MB发生发展过程中的功能,并提出了MB的潜在治疗方法。


原始出处:

Xue, P., Huang, S., Han, X. et al. Exosomal miR-101-3p and miR-423-5p inhibit medulloblastoma tumorigenesis through targeting FOXP4 and EZH2. Cell Death Differ (22 July 2021).

 

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    2022-01-21 smallant2002
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[GetPortalCommentsPageByObjectIdResponse(id=1930835, encodeId=20271930835f6, content=<a href='/topic/show?id=22f61180211' target=_blank style='color:#2F92EE;'>#miR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11802, encryptionId=22f61180211, topicName=miR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a27288, createdName=smallant2002, createdTime=Fri Jan 21 04:54:35 CST 2022, time=2022-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2030820, encodeId=01f9203082035, content=<a href='/topic/show?id=71353e8964f' target=_blank style='color:#2F92EE;'>#发生发展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37896, encryptionId=71353e8964f, topicName=发生发展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Mon Nov 08 15:54:35 CST 2021, time=2021-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872255, encodeId=881d18e2255f4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Feb 01 11:54:35 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962567, encodeId=bbe0196256e36, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, 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=Sat Aug 07 19:54:35 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062138, encodeId=6be3106213806, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220625/6f4f075937de4c5d9fc7ab3a1bc6d8c2/13a8a29e67044698af1fb74276589093.jpg, createdBy=b5c55099112, createdName=D-House, createdTime=Wed Oct 20 05:08:50 CST 2021, time=2021-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772397, encodeId=88cb1e723979e, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, 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style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Sun Jul 25 15:54:35 CST 2021, time=2021-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479398, encodeId=aa8614e9398bc, content=<a href='/topic/show?id=107610211e67' target=_blank style='color:#2F92EE;'>#髓母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102117, encryptionId=107610211e67, topicName=髓母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f2f7518854, createdName=124986d2m11暂无昵称, createdTime=Sun Jul 25 15:54:35 CST 2021, time=2021-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531751, encodeId=a5e41531e5119, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, 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=Sun Jul 25 15:54:35 CST 2021, time=2021-07-25, status=1, ipAttribution=)]
    2021-08-07 维他命
  5. 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style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Sun Jul 25 15:54:35 CST 2021, time=2021-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479398, encodeId=aa8614e9398bc, content=<a href='/topic/show?id=107610211e67' target=_blank style='color:#2F92EE;'>#髓母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102117, encryptionId=107610211e67, topicName=髓母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f2f7518854, createdName=124986d2m11暂无昵称, createdTime=Sun Jul 25 15:54:35 CST 2021, time=2021-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531751, encodeId=a5e41531e5119, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, 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=Sun Jul 25 15:54:35 CST 2021, time=2021-07-25, status=1, ipAttribution=)]
    2021-10-20 D-House

    学习了

    0

  6. 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  7. 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    2021-07-25 Homburg
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    2021-07-25 cy0328

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新的证据表明,泛素相关结构域蛋白2 (UBAC2)与恶性肿瘤的发生发展密切相关。然而,UBAC2在膀胱癌(BC)发展中的功能和潜在的分子机制尚未明确。

J Gastroenterology: 新型尿液microRNA可用于检测胃癌的发生

胃癌(GC)是世界范围内导致癌症死亡的最常见原因之一。但是,尚未建立可靠且无创的GC筛选方法。因此,本项研究旨在开发一种用于GC检测的生物标志物,该标志物由尿液microRNA(miRNA)组成。