MicroRNA-128-3p-mediated depletion of Drosha promotes lung cancer cell migration Journal Articles uri icon

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abstract

  • Alteration in microRNAs (miRNAs) expression is a frequent finding in human cancers. In particular, widespread miRNAs down-regulation is a hallmark of malignant transformation. In the present report, we showed that the miR-128-3p, which is up-regulated in lung cancer tissues, has Drosha and Dicer, two key enzymes of miRNAs processing, as the main modulation targets leading to the widespread down-regulation of miRNA expression. We observed that the miRNAs downregulation induced by miR-128-3p contributed to the tumorigenic properties of lung cancer cells. In particular, miR-128-3p-mediated miRNAs down-regulation contributed to aberrant SNAIL and ZEB1 expression thereby promoting the epithelial-to-mesenchymal transition (EMT) program. Drosha also resulted to be implicated in the control of migratory phenotype as its expression counteracted miR-128-3p functional effects. Our study provides mechanistic insights into the function of miR-128-3p as a key regulator of the malignant phenotype of lung cancer cells. This also enforces the remarkable impact of Drosha and Dicer alteration in cancer, and in particular it highlights a role for Drosha in non-small-cell lung cancer cells migration.

authors

  • Frixa, Tania
  • Sacconi, Andrea
  • Cioce, Mario
  • Roscilli, Giuseppe
  • Ferrara, Fabiana Fosca
  • Aurisicchio, Luigi
  • Pulito, Claudio
  • Telera, Stefano
  • Carosi, Mariantonia
  • Muti, Paola
  • Strano, Sabrina
  • Donzelli, Sara
  • Blandino, Giovanni

publication date

  • February 9, 2018