Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International University, Miami, FL, 33199, USA.
Biomolecular Sciences Institute, The Florida International University, Miami, FL, 33199, USA.
Sci Rep. 2021 Feb 24;11(1):4420. doi: 10.1038/s41598-021-83884-9.
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.
范可尼贫血（FA）途径对于人类细胞在 DNA 损伤后维持基因组完整性至关重要。该途径通过同源重组参与修复受损 DNA。FA 途径有缺陷的癌症预计对交联基治疗或 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 阵列研究了两个 FA 缺陷肺癌细胞和匹配的对照细胞、两个肺癌肿瘤和匹配的非肿瘤组织样本中 734 种不同 microRNA（miRNA）的表达情况，这些样本在 FA 途径中存在缺陷。使用实时 PCR 分析验证了选定的 miRNA 表达。在 734 种不同的 miRNA 中，发现了一组 miRNA 上调，包括一种重要的癌症相关 miRNA，miR-200C。miR-200C 已被报道为上皮-间充质转化（EMT）的负调节剂，通过靶向 ZEB1 和 ZEB2 转录因子促进 E-钙粘蛋白的上调，从而抑制细胞迁移和侵袭。与对照相比，FA 缺陷型肺癌中 miR-200C 增加。AmpliSeq 分析显示 ZEB1 和 ZEB2 mRNA 表达显著降低。我们的研究结果表明，miR-200C 可能在 FA 途径的下游调控中发挥非常重要的作用。
