MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers.

MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers.
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DOI:
10.1038/s41598-021-83884-9
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发表时间:
2021-02-24
期刊:
影响因子:
4.6
通讯作者:
Villalona-Calero MA
Villalona-Calero MA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Duan W;Tang S;Gao L;Dotts K;Fink A;Kalvala A;Aguila B;Wang QE;Villalona-Calero MA

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范可尼贫血(FA)途径是人类细胞在DNA损伤后维持基因组完整性所必需的。该途径通过同源重组参与修复受损的DNA。具有缺陷性FA通路的癌症预期对基于交联的疗法或PARP抑制剂更敏感。为了评估FA途径的下游效应物,我们使用NanoString nCounter miRNA阵列研究了734种不同的微小RNA(miRNA)在两种FA缺陷型肺癌细胞和匹配的对照细胞中的表达,沿着两种肺肿瘤和匹配的FA途径缺陷型非肿瘤组织样品。选择的miRNA表达用实时PCR分析验证。在734种不同的miRNA中,发现一组microRNA被上调,包括一种重要的癌症相关microRNA,miR-200 C。miRNA-200 C被报道为上皮-间质转化(EMT)的负调节因子,并通过靶向ZEB 1和ZEB 2转录因子促进E-cadherin的上调来抑制细胞迁移和侵袭。与对照组相比,FA缺陷型肺癌中的miRNA-200 C增加。AmpliSeq分析显示ZEB 1和ZEB 2 mRNA表达显著降低。我们的研究结果表明,miRNA-200 C可能在FA通路下游调控中发挥非常重要的作用。
The Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This pathway is involved in repairing damaged DNA through homologous recombination. Cancers with a defective FA pathway are expected to be more sensitive to cross-link based therapy or PARP inhibitors. To evaluate downstream effectors of the FA pathway, we studied the expression of 734 different micro RNAs (miRNA) using NanoString nCounter miRNA array in two FA defective lung cancer cells and matched control cells, along with two lung tumors and matched non-tumor tissue samples that were deficient in the FA pathway. Selected miRNA expression was validated with real-time PCR analysis. Among 734 different miRNAs, a cluster of microRNAs were found to be up-regulated including an important cancer related micro RNA, miR-200C. MiRNA-200C has been reported as a negative regulator of epithelial-mesenchymal transition (EMT) and inhibits cell migration and invasion by promoting the upregulation of E-cadherin through targeting ZEB1 and ZEB2 transcription factors. miRNA-200C was increased in the FA defective lung cancers as compared to controls. AmpliSeq analysis showed significant reduction in ZEB1 and ZEB2 mRNA expression. Our findings indicate the miRNA-200C potentially play a very important role in FA pathway downstream regulation.
MicroRNA-200C的表达水平通过调节胃癌中的Zeb1/2和E-钙粘着蛋白的调节与细胞形态和组织学分化有关。
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