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

Alice Faversani; Stefano Amatori; Claudia Augello; Federico Colombo; Laura Porretti; Mirco Fanelli; Stefano Ferrero; Alessandro Palleschi; Pier Giuseppe Pelicci; Elena Belloni; Giulia Ercoli; Anna Degrassi; Marco Baccarin; Dario C Altieri; Valentina Vaira; Silvano Bosari

doi:10.18632/oncotarget.13933

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

Alice Faversani, Stefano Amatori, Claudia Augello, Federico Colombo, Laura Porretti, Mirco Fanelli, Stefano Ferrero, Alessandro Palleschi, Pier Giuseppe Pelicci, Elena Belloni, Giulia Ercoli, Anna Degrassi, Marco Baccarin, Dario C Altieri, Valentina Vaira, Silvano Bosari

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	7231-7247
Number of pages	17
Journal	Oncotarget
Volume	8
Issue number	5
DOIs	https://doi.org/10.18632/oncotarget.13933
Publication status	Published - Jan 31 2017

Keywords

A549 Cells
Animals
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic/genetics
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genes, ras
Humans
Kaplan-Meier Estimate
Lung Neoplasms/genetics
Male
Mice, Nude
Mice, Transgenic
MicroRNAs/genetics
Mutation
Neoplasm Invasiveness
Neoplastic Stem Cells/metabolism
PTEN Phosphohydrolase/genetics
Phosphatidylinositol 3-Kinase/metabolism
Prognosis
Proto-Oncogene Proteins c-akt/metabolism
Receptor, Notch1/genetics
Side-Population Cells/metabolism
Signal Transduction
Time Factors
Transfection
Tumor Burden

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10.18632/oncotarget.13933

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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, 31.01.2017, p. 7231-7247.

Research output: Contribution to journal › Article › peer-review

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. / miR-494-3p is a novel tumor driver of lung carcinogenesis. In: Oncotarget. 2017 ; Vol. 8, No. 5. pp. 7231-7247.

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title = "miR-494-3p is a novel tumor driver of lung carcinogenesis",

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.",

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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 - 2017/1/31

Y1 - 2017/1/31

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 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.

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 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.

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KW - Gene Regulatory Networks

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KW - Humans

KW - Kaplan-Meier Estimate

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KW - Side-Population Cells/metabolism

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EP - 7247

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 5

ER -

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

Abstract

Keywords

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