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Genes & Dev:科学家鉴别出可抑制致死性脑瘤癌基因表达的小RNA分子

2015-04-08 佚名 生物谷

近日,刊登在国际杂志Genes & Development上的一篇研究论文中,来自美国西北大学的研究人员通过研究发现,一种名为miR-182的小RNA分子可以抑制多形性胶质母细胞瘤(GBM)小鼠机体中的促癌基因的表达,而GBM是一类致死性难以治愈的脑瘤。 目前标准疗法药物主要是通过损伤DNA来阻断癌细胞再生,而新型方法则会阻断产生癌细胞的来源,即过表达特定蛋白的基因;Alexande

近日,刊登在国际杂志Genes & Development上的一篇研究论文中,来自美国西北大学的研究人员通过研究发现,一种名为miR-182的小RNA分子可以抑制多形性胶质母细胞瘤(GBM)小鼠机体中的促癌基因的表达,而GBM是一类致死性难以治愈的脑瘤。

目前标准疗法药物主要是通过损伤DNA来阻断癌细胞再生,而新型方法则会阻断产生癌细胞的来源,即过表达特定蛋白的基因;Alexander Stegh教授说道,我们发现名为miR-182的RNA分子可以作为胶质母细胞瘤的抑制子来减少多种促癌基因的表达;而在这项研究中研究者利用一种名为球形核酸(SNAs)的纳米结构来安全地将miR-182分子跨过血脑屏障运输抵达肿瘤细胞,在肿瘤细胞中其就可以同时靶向作用多种癌基因的表达从而增加癌细胞的死亡并且减少癌细胞的生长,SNAs包括多种DNA和RNA链,其紧密折叠后形成了纳米结构的中心区域。

研究者表示,SNAs或许是一种潜在的平台来帮助科学家们沉默特殊基因从而杀灭癌细胞,本文研究中miR-182分子可以抑制Bcl2L12的表达,Bcl2L12是一种癌基因,其可以阻断癌细胞响应化疗或放疗法而死亡,而miR-182分子也可以抑制另外两个癌基因c-Met和HIF2A的表达,下一步研究者将计划开发一种方法使miR-182可以达到其它特殊的靶点位置。

研究者利用SNAs设计出了一种运输miR-182的新方法,小型的金纳米颗粒可以同miR-182序列偶联,其可以跨越血脑屏障进而在脑部肿瘤位点进行积累,在肿瘤患处就可以靶向作用癌基因的表达,进而调节癌细胞的生长和分化,降低肿瘤的增殖,同时延长小鼠模型的寿命。SNAs所具有的特性可以使其不给机体免疫系统带来毒性和激活作用的前提下,同时到达到目的细胞;而本文中所用的基因沉默技术在此前进行的脑瘤疗法研究中并未阐明,研究者表示,这些纳米颗粒,基于SNAs的microRNA分子或许也可以在其它癌症及遗传性疾病的研究中利用基因沉默的技术来进行机制的解析。

最后研究者Stegh表示,未来还需要进行额外的研究,在进入胶质母细胞瘤患者临床试验的研究前对miR-182及纳米运输技术的安全性进行检测,我们希望在后期研究中将miR-182同当前疗法结合起来进行小鼠模型的研究观察联合疗法对小鼠的疗效。

原始出处:

Fotini M. Kouri, Lisa A. Hurley, Weston L. Danie, et al.miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma[J].Genes & Dev, April 1, 2015, 29 (7):732-745; doi:10.1101/gad.257394.114

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    2015-10-27 fzwish20000
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    2015-05-30 cy0324
  4. [GetPortalCommentsPageByObjectIdResponse(id=1982217, encodeId=6787198221ec7, content=<a href='/topic/show?id=13b658e849' target=_blank style='color:#2F92EE;'>#Dev#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5878, encryptionId=13b658e849, topicName=Dev)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bcaa382, createdName=fzwish20000, createdTime=Tue Oct 27 05:14:00 CST 2015, time=2015-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1793406, encodeId=88091e9340616, content=<a href='/topic/show?id=b70615551ff' target=_blank style='color:#2F92EE;'>#RNA分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15551, encryptionId=b70615551ff, topicName=RNA分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4f2c2500194, createdName=446798725_87912765, createdTime=Tue Jun 09 14:14:00 CST 2015, time=2015-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048652, encodeId=bfdb20486526b, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat May 30 22:14:00 CST 2015, time=2015-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24731, encodeId=174224e31d5, content=不错,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=ac181616815, createdName=ljjj1053, createdTime=Sun May 24 12:51:00 CST 2015, time=2015-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1275655, encodeId=e41012e56557d, content=<a href='/topic/show?id=aad38494640' target=_blank style='color:#2F92EE;'>#脑瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84946, encryptionId=aad38494640, topicName=脑瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373a131, createdName=jxrzshh, createdTime=Fri Apr 10 00:14:00 CST 2015, time=2015-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348002, encodeId=9361134800219, content=<a href='/topic/show?id=d61b418860a' target=_blank style='color:#2F92EE;'>#基因表达#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41886, encryptionId=d61b418860a, topicName=基因表达)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Fri Apr 10 00:14:00 CST 2015, time=2015-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373879, encodeId=cfd413e38790b, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Fri Apr 10 00:14:00 CST 2015, time=2015-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568241, encodeId=d1081568241f6, content=<a href='/topic/show?id=569d8644eb9' target=_blank style='color:#2F92EE;'>#致死性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86447, encryptionId=569d8644eb9, topicName=致死性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae1815335551, createdName=andy2092, createdTime=Fri Apr 10 00:14:00 CST 2015, time=2015-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604199, encodeId=0c77160419935, content=<a href='/topic/show?id=a2df4684e9a' target=_blank style='color:#2F92EE;'>#小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46847, encryptionId=a2df4684e9a, topicName=小RNA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Fri Apr 10 00:14:00 CST 2015, time=2015-04-10, status=1, ipAttribution=)]
    2015-05-24 ljjj1053

    不错,学习了

    0

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    2015-04-10 jxrzshh
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    2015-04-10 heli0118

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