By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer.
By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer.
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hsa-miR-526b 通过下调 Ku80 抑制非小细胞肺癌
DOI：
10.18632/oncotarget.2808
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发表时间：
2015-01-30
期刊：
影响因子：
--
通讯作者：
Wei S
中科院分区：
文献类型：
--
作者：
Zhang ZY;Fu SL;Xu SQ;Zhou X;Liu XS;Xu YJ;Zhao JP;Wei S
Ku 80参与DNA双链断裂（DSB）修复。Ku 80在肺癌组织中过表达，但其分子机制尚未研究。我们发现miRNA hsa-miR-526 b与Ku 80 mRNA的3′-UTR结合，从而降低了Ku 80在NSCLC细胞中的表达。与相应的非肿瘤组织相比，Hsa-miR-526 b在NSCLC组织中下调，其表达与Ku 80上调呈负相关。Ku 80过表达和hsa-miR-526 b下调与NSCLC患者的不良临床结局相关。Hsa-miR-526 b抑制NSCLC细胞增殖、克隆形成，并诱导细胞周期停滞和凋亡。Hsa-miR-526 b抑制异种移植物和原位肺肿瘤生长。此外，Ku 80在NSCLC细胞中的敲低抑制了体外和体内的肿瘤特性，类似于hsa-miR-526 b过表达。一致的是，Ku 80恢复在体外和体内部分逆转了hsa-miR-526 b诱导的NSCLC细胞细胞周期停滞和细胞凋亡。此外，hsa-miR-526 b过表达或Ku 80敲低可增加p53和p21 CIP 1/WAF 1的表达。这些发现表明hsa-miR-526 b是癌症治疗的潜在靶点。
Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed in lung cancer tissues, yet, molecular mechanisms have not been examined. We identified that miRNA, hsa-miR-526b, is bound to the 3′-UTR of Ku80 mRNA, thus decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in NSCLC tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Overexpression of Ku80 and downregulation of hsa-miR-526b were associated with poor clinical outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation, clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo. In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
DOI：
10.1073/pnas.022649699
发表时间：
2002-01-22
影响因子：
11.1
作者：
Li, G;Nelsen, C;Hendrickson, EA
通讯作者：
Hendrickson, EA
影响因子：
3.7
作者：
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影响因子：
3.6
作者：
Korrapati, V;Gaffney, M;Mott, F E
通讯作者：
Mott, F E
影响因子：
2.9
作者：
Nian W;Ao X;Wu Y;Huang Y;Shao J;Wang Y;Chen Z;Chen F;Wang D
通讯作者：
Wang D