skip to main content

MicroRNA-20a-mediated loss of autophagy contributes to breast tumorigenesis by promoting genomic damage and instability

L Liu ; J He ; X Wei ; G Wan ; Y Lao ; W Xu ; Z Li ; H Hu ; Z Hu ; X Luo ; J Wu ; W Xie ; Y Zhang ; N Xu

Oncogene, 2017 [Periódico revisado por pares]

Texto completo disponível

Citações Citado por
  • Título:
    MicroRNA-20a-mediated loss of autophagy contributes to breast tumorigenesis by promoting genomic damage and instability
  • Autor: L Liu ; J He ; X Wei ; G Wan ; Y Lao ; W Xu ; Z Li ; H Hu ; Z Hu ; X Luo ; J Wu ; W Xie ; Y Zhang ; N Xu
  • Assuntos: Genomes -- Analysis ; Medical Research -- Analysis ; Cancer Genetics -- Analysis ; Cancer Genetics -- Genetic Aspects ; Dna Repair -- Analysis ; Tumors -- Analysis ; Tumors -- Genetic Aspects ; Genes -- Analysis ; Gene Expression -- Analysis ; Genomics -- Analysis ; Microrna -- Analysis ; Gene Mutation -- Analysis
  • É parte de: Oncogene, 2017
  • Descrição: Gene expression analysis of The Cancer Genome Atlas (TCGA) breast cancer data set show that miR-20a is upregulated in human breast cancer, especially in triple-negative subtype. Gene Set Enrichment Analysis suggests that miR-20a expression negatively correlates with the autophagy/lysosome pathway. We report here that miR-20a inhibits the basal and nutrient starvation-induced autophagic flux and lysosomal proteolytic activity, increases intracellular reactive oxygen species levels and DNA damage response by targeting several key regulators of autophagy, including BECN1, ATG16L1 and SQSTM1. Re-introduction of exogenous BECN1, ATG16L1 or SQSTM1 reverses the inhibitory effect of miR-20a on autophagy and decreases DNA damage. A negative correlation between miR-20a and its target genes is observed in breast cancer tissues. Lower levels of BECN1, ATG16L1 and SQSTM1 are more common in triple-negative cancers than in other subtypes. High levels of miR-20a also associate with higher frequency of copy-number alterations and DNA mutations in breast cancer patients. Further studies in a xenograft mouse model show that miR-20a promotes tumor initiation and tumor growth. Collectively, these findings suggest that miR-20a-mediated autophagy defect might be a new mechanism underlying the oncogenic function of miRNA during breast tumorigenesis. Oncogene (2017) 36, 5874-5884; doi: 10.1038/onc.2017.193; published online 19 June 2017

Buscando em bases de dados remotas. Favor aguardar.