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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 349-364 |
| Number of pages | 16 |
| Journal | Journal of Clinical Investigation |
| Volume | 126 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 4 2016 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer. / Edmonds, Mick D.; Boyd, Kelli L.; Moyo, Tamara; Mitra, Ramkrishna; Duszynski, Robert; Arrate, Maria Pia; Chen, Xi; Zhao, Zhongming; Blackwell, Timothy S.; Andl, Thomas; Eischen, Christine M.
In: Journal of Clinical Investigation, Vol. 126, No. 1, 04.01.2016, p. 349-364.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer
AU - Edmonds, Mick D.
AU - Boyd, Kelli L.
AU - Moyo, Tamara
AU - Mitra, Ramkrishna
AU - Duszynski, Robert
AU - Arrate, Maria Pia
AU - Chen, Xi
AU - Zhao, Zhongming
AU - Blackwell, Timothy S.
AU - Andl, Thomas
AU - Eischen, Christine M.
PY - 2016/1/4
Y1 - 2016/1/4
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI82720
DO - 10.1172/JCI82720
M3 - Article
VL - 126
SP - 349
EP - 364
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 1
ER -