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- Title
MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer.
- Authors
Edmonds, Mick D.; Boyd, Kelli L.; Moyo, Tamara; Mitra, Ramkrishna; Duszynski, Robert; Arrate, Maria Pia; Xi Chen; Zhongming Zhao; Blackwell, Timothy S.; Andl, Thomas; Eischen, Christine M.; Chen, Xi; Zhao, Zhongming
- 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.
- Subjects
MICRORNA; LUNG cancer &; genetics; ADENOCARCINOMA; CANCER prognosis; NEOPLASTIC cell transformation; MITOGEN-activated protein kinases; CELLULAR signal transduction; LABORATORY mice; RNA physiology; ANIMAL experimentation; CELL lines; CELLS; LUNG tumors; MICE; GENETIC mutation; PROTEINS; RESEARCH funding
- Publication
Journal of Clinical Investigation, 2016, Vol 126, Issue 1, p349
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI82720