Data from miR-21 Inhibition Reduces Liver Fibrosis and Prevents Tumor Development by Inducing Apoptosis of CD24+ Progenitor Cells
Year: 2023
Type: other
Abstract: 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 αv. 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. ©2015 AACR.
Authors: Jing Zhang, Jingjing Jiao, Silvia Cermelli, Kyle Muir, Kwang Hwa Jung, Ruhai Zou, Asif Rashid, Mihai Gagea, Sonya Zabludoff, Raghu Kalluri, Laura Beretta
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4392687758