MiR-155 is a liposarcoma oncogene that targets casein kinase-1α and enhances β-catenin signaling.

Abstract

Liposarcoma can be an aggressive, debilitating, and fatal malignancy. In this study, we identifed miRNAs associated with the differentiation status of liposarcoma to gain insight into the basis for its progression. miRNA expression profiles determined in human tumors and normal fat specimens identified a dedifferentiated tumor expression signature consisting of 35 miRNAs. Deregulated miRNA expression was confirmed in a second independent sample cohort. The miR-155 was the most overexpressed miRNA and functional investigations assigned an important role in the growth of dedifferentiated liposarcoma cell lines. Transient or stable knockdown of miR-155 retarded tumor cell growth, decreased colony formation, and induced G(1)-S cell-cycle arrest in vitro and blocked tumor growth in murine xenografts in vivo. We identified casein kinase 1α (CK1α) as a direct target of miR-155 control which enhanced β-catenin signaling and cyclin D1 expression, promoting tumor cell growth. In summary, our results point to important functions for miR-155 and β-catenin signaling in progression of liposarcoma, revealing mechanistic vulnerabilities that might be exploited for both prognostic and therapeutic purposes.

• Authors: Pingyu Zhang, Katelynn Bill, Juehui Liu, Eric Young, Tingsheng Peng, Svetlana Bolshakov, Aviad Hoffman, Yechun Song, Elizabeth G Demicco, Dolores Lopez Terrada, Chad J Creighton, Matthew L Anderson, Alexander J Lazar, George G Calin, Raphael E Pollock, Dina Lev
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 7 Pg. 1751-62 (Apr 01 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22350414 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• CTNNB1 protein, human
• MIRN155 microRNA, human
• MicroRNAs
• beta Catenin
• Cyclin D1
• Casein Kinase I

Topics

• Animals
• Base Sequence
• Casein Kinase I (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• Liposarcoma (genetics, pathology)
• Mice
• MicroRNAs (physiology)
• Molecular Sequence Data
• Oncogenes
• Signal Transduction (physiology)
• beta Catenin (physiology)