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Cell Death Dis:新型环状RNA circXPO1促进肺腺癌的发生发展

2020-12-12 MedSci原创 MedSci原创

肺癌是全球范围内肿瘤相关死亡的主要原因之一。肺腺癌(LUAD)作为肺癌的主要组织学类型,在中国,LUAD的发病率逐年增加。尽管目前已开发出了针对LUAD的新的治疗方法,但患者的5年生存率仅为12%至1

肺癌是全球范围内肿瘤相关死亡的主要原因之一。肺腺癌(LUAD)作为肺癌的主要组织学类型,在中国,LUAD的发病率逐年增加。尽管目前已开发出了针对LUAD的新的治疗方法,但患者的5年生存率仅为12%至15%。因此,进一步探索LUAD的分子机制和鉴定相应的生物标记物能够提高患者的治疗效果。

既往研究显示,非编码RNA(ncRNA)在各种类型的癌症中起着至关重要的作用。环状RNA(circRNA)作为一类独特的非编码RNA,在哺乳动物细胞和组织中具有独特的特性和功能。circRNA在多种疾病(包括癌症)中发挥调节作用,并行使众所周知的“ miRNA分子海绵”的功能。


然而,目前关于基因组改变区域的非编码RNA的研究很少,特别是circRNA。该研究前期通过RNA测序发现,在LUAD肿瘤组织中一些circRNA的表达水平上调。

circXPO1的转录本

研究人员在LUAD中发现了一种新的circRNA,circXPO1,其来自于一个公认的癌症治疗靶标XPO1。circXPO1是由XPO1基因的3号外显子和4号外显子反向剪接形成的。相比于相邻的非肿瘤组织,circXPO1在LUAD组织中高表达,而circXPO1的高表达水平与更差的总体生存率相关。


研究人员发现,circXPO1的表达水平与XPO1基因的拷贝数呈正相关。机制研究显示,circXPO1可以与IGF2BP1结合并增强CTNNB1 mRNA的稳定性,并最终促进LUAD的发生发展。在LUAD患者衍生的移植瘤模型中,在肿瘤内注射特异性的靶向circXPO1的胆固醇缀合siRNA能够有效的抑制肿瘤的生长。

circXPO1促进LUAD肿瘤的生长

综上所述,这些结果表明,circXPO1对于LUAD的发生发展至关重要,其可能作为该疾病的不良预后和治疗的生物标志物。


原始出处:

Huang, Q., Guo, H., Wang, S. et al. A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1. Cell Death Dis 11, 1031 (02 December 2020).

 

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    2021-07-04 zhaojie88
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    2021-07-17 维他命
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    2020-12-14 cy0328
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    2020-12-13 Nebula-Qin

    肺腺癌(LUAD)作为肺癌的主要组织学类型,在中国,LUAD的发病率逐年增加。尽管目前已开发出了针对LUAD的新的治疗方法,但患者的5年生存率仅为12%至15%。#肺腺癌##环状RNA#

    0

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    2020-12-12 瓜虫

    学习了

    0

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    2020-12-12 ms4000001626131795

    学习了

    0

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