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