< i > In vivo < /i > miRNA knockout screening identifies miR-190b as a novel tumor suppressor

by Hui Hong, Shun Yao, Yuanyuan Zhang, Yi Ye, Cheng Li, Liang Hu, Yihua Sun, Hsin-Yi Huang, Hongbin Ji MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function inde novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human lung cancer miRNA database, we identified 16 downregulated miRNAs associated with malignant progression and performed individual knockout with dgRNA system inKrasG12D/Trp53L/L (KP) mouse model. Using thisin vivo knockout screening, we identified miR-30b and miR-146a, which has been previously reported as tumor suppressors and miR-190b, a new tumor-suppressive miRNA in lung cancer development. Over-expression of miR-190b inKP model as well as human lung cancer cell lines significantly suppressed malignant progression. We further found that miR-190b targeted theHus1 gene and knockout ofHus1 inKP model dramatically suppressed lung tumorigenesis. Collectively, our study developed anin vivo miRNA knockout platform for functionally screening in GEMM and identified miR-190b as a new tumor suppressor in lung cancer.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research