miR-221 overexpression contributes to liver tumorigenesis

Pineau, P., Volinia, S., McJunkin, K., Marchio, A., Battiston, C., Terris, B., Mazzaferro, V., Lowe, S. W., Croce, C. M., Dejean, A. (January 2010) miR-221 overexpression contributes to liver tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 107 (1). pp. 264-269. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/20018759
DOI: 10.1073/pnas.0907904107

Abstract

MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment.

Item Type: Paper
Uncontrolled Keywords: hepatocarcinogenesis microRNA antagomiRs mouse model DDIT4 HUMAN HEPATOCELLULAR-CARCINOMA MICRORNA EXPRESSION TUMOR-SUPPRESSOR CELL LINES CANCER GENE IDENTIFICATION PROLIFERATION MECHANISMS MIR-34A
Subjects: diseases & disorders > cancer > cancer types > breast cancer
diseases & disorders > cancer > cancer types > liver cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA

organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Lowe lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Watson School > Publications
Depositing User: CSHL Librarian
Date: 5 January 2010
Date Deposited: 05 Oct 2011 14:13
Last Modified: 05 Jan 2018 19:44
PMCID: PMC2806773
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15506

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