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 journalArticle

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 languageEnglish
Pages (from-to)7231-7247
Number of pages17
JournalOncotarget
Volume8
Issue number5
DOIs
Publication statusPublished - Jan 31 2017

Fingerprint

Lung Neoplasms
Carcinogenesis
Lung
Neoplasms
MicroRNAs
Neoplastic Stem Cells
Phosphatidylinositol 3-Kinases
Cell Movement
Stem Cells
Chromosomes
Survival
Population
Genes
Therapeutics

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

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, 31.01.2017, p. 7231-7247.

Research output: Contribution to journalArticle

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.
@article{028b9468277f47708b2a87a446791fa0,
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.",
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",
author = "Alice Faversani and Stefano Amatori and Claudia Augello and Federico Colombo and Laura Porretti and Mirco Fanelli and Stefano Ferrero and Alessandro Palleschi and Pelicci, {Pier Giuseppe} and Elena Belloni and Giulia Ercoli and Anna Degrassi and Marco Baccarin and Altieri, {Dario C} and Valentina Vaira and Silvano Bosari",
year = "2017",
month = "1",
day = "31",
doi = "10.18632/oncotarget.13933",
language = "English",
volume = "8",
pages = "7231--7247",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "5",

}

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 - 2017/1/31

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.

KW - A549 Cells

KW - Animals

KW - Cell Movement

KW - Cell Proliferation

KW - Cell Transformation, Neoplastic/genetics

KW - Disease Models, Animal

KW - Gene Expression Regulation, Neoplastic

KW - Gene Regulatory Networks

KW - Genes, ras

KW - Humans

KW - Kaplan-Meier Estimate

KW - Lung Neoplasms/genetics

KW - Male

KW - Mice, Nude

KW - Mice, Transgenic

KW - MicroRNAs/genetics

KW - Mutation

KW - Neoplasm Invasiveness

KW - Neoplastic Stem Cells/metabolism

KW - PTEN Phosphohydrolase/genetics

KW - Phosphatidylinositol 3-Kinase/metabolism

KW - Prognosis

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - Receptor, Notch1/genetics

KW - Side-Population Cells/metabolism

KW - Signal Transduction

KW - Time Factors

KW - Transfection

KW - Tumor Burden

U2 - 10.18632/oncotarget.13933

DO - 10.18632/oncotarget.13933

M3 - Article

C2 - 27980227

VL - 8

SP - 7231

EP - 7247

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 5

ER -