title: 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.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Pingyu
authors.initials: P
authors.lastname: Zhang
authors.forename: Katelynn
authors.initials: K
authors.lastname: Bill
authors.forename: Juehui
authors.initials: J
authors.lastname: Liu
authors.forename: Eric
authors.initials: E
authors.lastname: Young
authors.forename: Tingsheng
authors.initials: T
authors.lastname: Peng
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bolshakov
authors.forename: Aviad
authors.initials: A
authors.lastname: Hoffman
authors.forename: Yechun
authors.initials: Y
authors.lastname: Song
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Demicco
authors.forename: Dolores Lopez
authors.initials: DL
authors.lastname: Terrada
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Anderson
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.forename: George G
authors.initials: GG
authors.lastname: Calin
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
authors.forename: Dina
authors.initials: D
authors.lastname: Lev
mesh_terms: D000818:Animals; D001483:Base Sequence; D047389:Casein Kinase I / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008080:Liposarcoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D008969:Molecular Sequence Data; D009857:Oncogenes; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: C495270:CTNNB1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D019938:Cyclin D1; D047389:Casein Kinase I