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 cellrelated 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.
| Original language | English |
|---|---|
| Pages (from-to) | 7231-7247 |
| Number of pages | 17 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2017 |
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Keywords
- miR-494-3p
- MiRNA
- NOTCH1
- NSCLC
- Stem cells
ASJC Scopus subject areas
- Oncology
Cite this
miR-494-3p is a novel tumor driver of lung carcinogenesis. / Faversani, Alice; Amatori, Stefano; Augello, Claudia; Colombo, Federico; Porretti, Laura; Fanelli, Mirco; Ferrero, Stefano; Palleschi, Alessandro; Pelicci, Pier Giuseppe; Belloni, Elena; Ercoli, Giulia; Degrassi, Anna; Baccarin, Marco; Altieri, Dario C.; Vaira, Valentina; Bosari, Silvano.
In: Oncotarget, Vol. 8, No. 5, 2017, p. 7231-7247.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - miR-494-3p is a novel tumor driver of lung carcinogenesis
AU - Faversani, Alice
AU - Amatori, Stefano
AU - Augello, Claudia
AU - Colombo, Federico
AU - Porretti, Laura
AU - Fanelli, Mirco
AU - Ferrero, Stefano
AU - Palleschi, Alessandro
AU - Pelicci, Pier Giuseppe
AU - Belloni, Elena
AU - Ercoli, Giulia
AU - Degrassi, Anna
AU - Baccarin, Marco
AU - Altieri, Dario C.
AU - Vaira, Valentina
AU - Bosari, Silvano
PY - 2017
Y1 - 2017
N2 - 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 cellrelated 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.
AB - 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 cellrelated 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.
KW - miR-494-3p
KW - MiRNA
KW - NOTCH1
KW - NSCLC
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=85018929292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018929292&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13933
DO - 10.18632/oncotarget.13933
M3 - Article
AN - SCOPUS:85018929292
VL - 8
SP - 7231
EP - 7247
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 5
ER -