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

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

来源：Oncotarget, 2017, 8(12): 19172-19191.

DOI：10.18632/oncotarget.13432

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

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.

• 出版日期2017-3-21