Analysis of miRNA profiles identified miR-196a as a crucial mediator of aberrant PI3K/AKT signaling in lung cancer cells

Ilaria Guerriero, Daniela D'Angelo, Pierlorenzo Pallante, Mafalda Santos, Marianna Scrima, Donatella Malanga, Carmela De Marco, Maria Ravo, Alessandro Weisz, Carmelo Laudanna, Michele Ceccarelli, Geppino Falco, Antonia Rizzuto, Giuseppe Viglietto

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11 Citations (Scopus)

Abstract

Hyperactivation of the PI3K/AKT pathway is observed in most human cancer including lung carcinomas. Here we have investigated the role of miRNAs as downstream targets of activated PI3K/AKT signaling in Non Small Cell Lung Cancer (NSCLC). To this aim, miRNA profiling was performed in human lung epithelial cells (BEAS-2B) expressing active AKT1 (BEAS-AKT1-E17K), active PI3KCA (BEAS-PIK3CA-E545K) or with silenced PTEN (BEAS-shPTEN). Twenty-four differentially expressed miRNAs common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells were identified through this analysis, with miR-196a being the most consistently up-regulated miRNA. Interestingly, miR-196a was significantly overexpressed also in human NSCLC-derived cell lines (n=11) and primary lung cancer samples (n=28). By manipulating the expression of miR-196a in BEAS-2B and NCI-H460 cells, we obtained compelling evidence that this miRNA acts downstream the PI3K/AKT pathway, mediating some of the proliferative, pro-migratory and tumorigenic activity that this pathway exerts in lung epithelial cells, possibly through the regulation of FoxO1, CDKN1B (hereafter p27) and HOXA9.

Original languageEnglish
Pages (from-to)19172-19191
Number of pages20
JournalOncotarget
Volume8
Issue number12
DOIs
Publication statusPublished - 2017
Externally publishedYes

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Keywords

  • microRNA
  • MiR-196a
  • NSCLC
  • PI3K/AKT

ASJC Scopus subject areas

  • Oncology

Cite this

Guerriero, I., D'Angelo, D., Pallante, P., Santos, M., Scrima, M., Malanga, D., De Marco, C., Ravo, M., Weisz, A., Laudanna, C., Ceccarelli, M., Falco, G., Rizzuto, A., & Viglietto, G. (2017). Analysis of miRNA profiles identified miR-196a as a crucial mediator of aberrant PI3K/AKT signaling in lung cancer cells. Oncotarget, 8(12), 19172-19191. https://doi.org/10.18632/oncotarget.13432