Lung cancer is the leading cause of tumor-related death worldwide and more efforts are needed to elucidate lung carcinogenesis. Here we investigated the expression of 641 miRNAs in lung tumorigenesis in a K-Ras(+/LSLG12Vgeo);RERTn(ert/ert) mouse model and 113 human tumors. The conserved miRNA cluster on chromosome 12qF1 was significantly and progressively upregulated during murine lung carcinogenesis. In particular, miR-494-3p expression was correlated with lung cancer progression in mice and with worse survival in lung cancer patients. Mechanistically, ectopic expression of miR-494-3p in A549 lung cancer cells boosted the tumor-initiating population, enhanced cancer cell motility, and increased the expression of stem cell-related genes. Importantly, miR-494-3p improved the ability of A549 cells to grow and metastasize in vivo, modulating NOTCH1 and PTEN/PI3K/AKT signaling.Overall, these data identify miR-494-3p as a key factor in lung cancer onset and progression and possible therapeutic target.

miR-494-3p is a novel tumor driver of lung carcinogenesis / A. Faversani, S. Amatori, C. Augello, F. Colombo, L. Porretti, M. Fanelli, S. Ferrero, A. Palleschi, P.G. Pelicci, E. Belloni, G. Ercoli, A. Degrassi, M. Baccarin, D.C. Altieri, V. Vaira, S. Bosari. - In: ONCOTARGET. - ISSN 1949-2553. - 8:5(2017), pp. 7231-7247.

miR-494-3p is a novel tumor driver of lung carcinogenesis

A. Faversani
Primo
;
C. Augello;S. Ferrero;A. Palleschi;P.G. Pelicci;V. Vaira
;
S. Bosari
Ultimo
2017

Abstract

Lung cancer is the leading cause of tumor-related death worldwide and more efforts are needed to elucidate lung carcinogenesis. Here we investigated the expression of 641 miRNAs in lung tumorigenesis in a K-Ras(+/LSLG12Vgeo);RERTn(ert/ert) mouse model and 113 human tumors. The conserved miRNA cluster on chromosome 12qF1 was significantly and progressively upregulated during murine lung carcinogenesis. In particular, miR-494-3p expression was correlated with lung cancer progression in mice and with worse survival in lung cancer patients. Mechanistically, ectopic expression of miR-494-3p in A549 lung cancer cells boosted the tumor-initiating population, enhanced cancer cell motility, and increased the expression of stem cell-related genes. Importantly, miR-494-3p improved the ability of A549 cells to grow and metastasize in vivo, modulating NOTCH1 and PTEN/PI3K/AKT signaling.Overall, these data identify miR-494-3p as a key factor in lung cancer onset and progression and possible therapeutic target.
NOTCH1; NSCLC; miR-494-3p; miRNA; stem cells
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
Settore BIO/11 - Biologia Molecolare
miRNA and prostate cancer: new disease biomarkers and therapeutic options
14-dic-2016
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/465173
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