title: Expression of CD44 3'-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis.
abstract: The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed.
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto M4N 3M5, Canada.
authors.forename: Zina
authors.initials: Z
authors.lastname: Jeyapalan
authors.forename: Zhaoqun
authors.initials: Z
authors.lastname: Deng
authors.forename: Tatiana
authors.initials: T
authors.lastname: Shatseva
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.forename: Chengyan
authors.initials: C
authors.lastname: He
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D002460:Cell Line; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D018960:Hyaluronan Receptors; D035683:MicroRNAs; D020764:cdc42 GTP-Binding Protein