{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:11:38Z","timestamp":1775023898681,"version":"3.50.1"},"reference-count":38,"publisher":"American Association for Cancer Research (AACR)","issue":"9","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03b1v. 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\u201367. \u00a92015 AACR.<\/jats:p>","DOI":"10.1158\/0008-5472.can-14-1254","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T23:02:20Z","timestamp":1426287740000},"page":"1859-1867","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["miR-21 Inhibition Reduces Liver Fibrosis and Prevents Tumor Development by Inducing Apoptosis of CD24+ Progenitor Cells"],"prefix":"10.1158","volume":"75","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas."}]},{"given":"Jingjing","family":"Jiao","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas."}]},{"given":"Silvia","family":"Cermelli","sequence":"additional","affiliation":[{"name":"2Molecular Diagnostics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington."}]},{"given":"Kyle","family":"Muir","sequence":"additional","affiliation":[{"name":"2Molecular Diagnostics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington."}]},{"given":"Kwang Hwa","family":"Jung","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas."}]},{"given":"Ruhai","family":"Zou","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas."},{"name":"3State Key Laboratory of Oncology in Southern China, Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China."}]},{"given":"Asif","family":"Rashid","sequence":"additional","affiliation":[{"name":"4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas."}]},{"given":"Mihai","family":"Gagea","sequence":"additional","affiliation":[{"name":"5Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas."}]},{"given":"Sonya","family":"Zabludoff","sequence":"additional","affiliation":[{"name":"6Regulus Therapeutics, Inc, San Diego, California."}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"7Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas."}]},{"given":"Laura","family":"Beretta","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas."},{"name":"2Molecular Diagnostics Program, Public Health Sciences Division, Fred 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