title: MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer.
abstract: MicroRNA (miR) are important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to lung tumorigenesis. Here, we determined that miR-31 is overexpressed in human lung adenocarcinoma and this overexpression independently correlates with decreased patient survival. We developed a transgenic mouse model that allows for lung-specific expression of miR-31 to test the oncogenic potential of miR-31 in the lung. Using this model, we observed that miR-31 induction results in lung hyperplasia, followed by adenoma formation and later adenocarcinoma development. Moreover, induced expression of miR-31 in mice cooperated with mutant KRAS to accelerate lung tumorigenesis. We determined that miR-31 regulates lung epithelial cell growth and identified 6 negative regulators of RAS/MAPK signaling as direct targets of miR-31. Our study distinguishes miR-31 as a driver of lung tumorigenesis that promotes mutant KRAS-mediated oncogenesis and reveals that miR-31 directly targets and reduces expression of negative regulators of RAS/MAPK signaling.
authors.forename: Mick D
authors.initials: MD
authors.lastname: Edmonds
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.forename: Tamara
authors.initials: T
authors.lastname: Moyo
authors.forename: Ramkrishna
authors.initials: R
authors.lastname: Mitra
authors.forename: Robert
authors.initials: R
authors.lastname: Duszynski
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Arrate
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eischen
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009154:Mutation; D041681:NIH 3T3 Cells; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D018631:ras Proteins / Q000502:physiology
chemical_list: C117307:KRAS protein, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins