title: Analysis of miRNA profiles identified miR-196a as a crucial mediator of aberrant PI3K/AKT signaling in lung cancer cells.
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.
authors.affiliation: Biogems.c.ar.l., Istituto di Ricerche Genetiche "Gaetano Salvatore", Ariano Irpino (Avellino), Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guerriero
authors.affiliation: Istituto per l'Endocrinologia e l'Oncologia Sperimentale, IEOS-CNR, c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università "Federico II" of Napoli, Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Angelo
authors.affiliation: Istituto per l'Endocrinologia e l'Oncologia Sperimentale, IEOS-CNR, c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università "Federico II" of Napoli, Napoli, Italy.
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.affiliation: Biogems.c.ar.l., Istituto di Ricerche Genetiche "Gaetano Salvatore", Ariano Irpino (Avellino), Italy.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Santos
authors.affiliation: Biogems.c.ar.l., Istituto di Ricerche Genetiche "Gaetano Salvatore", Ariano Irpino (Avellino), Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Scrima
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Malanga
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia of Catanzaro, Catanzaro,Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: De Marco
authors.affiliation: Laboratorio di Medicina Molecolare e Genomica, Dipartimentodi Medicina e Chirurgia, Università di Salerno, Baronissi, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ravo
authors.affiliation: Laboratorio di Medicina Molecolare e Genomica, Dipartimentodi Medicina e Chirurgia, Università di Salerno, Baronissi, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Laudanna
authors.affiliation: Biogems.c.ar.l., Istituto di Ricerche Genetiche "Gaetano Salvatore", Ariano Irpino (Avellino), Italy.|Department of Biological and Environmental Studies, Università del Sannio, Benevento, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ceccarelli
authors.affiliation: Biogems.c.ar.l., Istituto di Ricerche Genetiche "Gaetano Salvatore", Ariano Irpino (Avellino), Italy.
authors.forename: Geppino
authors.initials: G
authors.lastname: Falco
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Rizzuto
authors.affiliation: Biogems.c.ar.l., Istituto di Ricerche Genetiche "Gaetano Salvatore", Ariano Irpino (Avellino), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viglietto
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: NSCLC; PI3K/AKT; miR-196a; microRNA