| First Author | Zhang J | Year | 2015 |
| Journal | Cancer Res | Volume | 75 |
| Issue | 9 | Pages | 1859-67 |
| PubMed ID | 25769721 | Mgi Jnum | J:220684 |
| Mgi Id | MGI:5635939 | Doi | 10.1158/0008-5472.CAN-14-1254 |
| Citation | Zhang J, et al. (2015) miR-21 Inhibition Reduces Liver Fibrosis and Prevents Tumor Development by Inducing Apoptosis of CD24+ Progenitor Cells. Cancer Res 75(9):1859-67 |
| abstractText | miR-21 is upregulated in hepatocellular carcinoma and intrahepatic cholangiocarcinoma, where it is associated with poor prognosis. Here, we offer preclinical evidence that miR-21 offers a therapeutic and chemopreventive target in these liver cancers. In mice with hepatic deletion of Pten, anti-miR-21 treatment reduced liver tumor growth and prevented tumor development. These effects were accompanied with a decrease in liver fibrosis and a concomitant reduction of CD24(+) liver progenitor cells and S100A4(+) cancer-associated stromal cells. Notch2 inhibition also occurred in tumors following anti-miR-21 treatment. We further showed that miR-21 is necessary for the survival of CD24(+) progenitor cells, a cellular phenotype mediated by Notch2, osteopontin, and integrin alphav. Our results identify miR-21 as a key regulator of tumor-initiating cell survival, malignant development, and growth in liver cancer, highlighting the role of CD24(+) cells in the expansion of S100A4(+) cancer-associated stromal cells and associated liver fibrosis. Cancer Res; 75(9); 1859-67. (c)2015 AACR. |
