MicroRNA-128-3p-mediated depletion of Drosha promotes lung cancer cell migration

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

Research output: Contribution to journalArticlepeer-review

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-smallcell lung cancer cells migration.

Original languageEnglish
Pages (from-to)293-304
Number of pages12
JournalCarcinogenesis
Volume39
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

ASJC Scopus subject areas

  • Cancer Research

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