title: The intermediate filament vimentin mediates microRNA miR-378 function in cellular self-renewal by regulating the expression of the Sox2 transcription factor.
abstract: MicroRNAs are short noncoding RNAs that are implicated in cell self- renewal and cancer development. We show that miR-378 is up-regulated in human cancers and found that tumor cells transfected with miR-378 acquired properties of tumor stem cells, including cell self-renewal. Overexpression of miR-378 enhanced cell survival and colony formation. Isolated from a single-cell colony, the miR-378-expressing cells formed tumors in nude mice at low cell densities. These cells expressed higher levels of miR-378 and formed more and larger spheres and colonies. We found that the miR-378-expressing cells contained a large number of side population cells and could undergo differentiation. Cells transfected with miR-378 expressed increased levels of Sox2. Expression of miR-378 and Sox2 was found correlated significantly in cancer cell lines and in cancer patient specimens. We also observed opposite levels of vimentin in the cancer cell lines and human breast carcinoma specimens. We further demonstrated that vimentin is a target of miR-378, and ectopic transfection of vimentin inhibited Sox2 expression, resulting in decreased cell survival. Silencing vimentin promoted Sox2 expression and cell survival. Our study demonstrates that miR-378 is a regulator of stem cell marker Sox2 by targeting vimentin, which may serve as a new tool in studying the role of stem cells in tumorigenesis.
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.
authors.forename: Zhaoqun
authors.initials: Z
authors.lastname: Deng
authors.forename: William W
authors.initials: WW
authors.lastname: Du
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.forename: Sze Wan
authors.initials: SW
authors.lastname: Shan
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Jichun
authors.initials: J
authors.lastname: Ma
authors.forename: Zina Jeyapalan
authors.initials: ZJ
authors.lastname: Rutnam
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology; D009389:Neovascularization, Pathologic; D019301:Oleic Acid / Q000494:pharmacology; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014746:Vimentin / Q000378:metabolism*
chemical_list: C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D055748:SOXB1 Transcription Factors; D014746:Vimentin; D019301:Oleic Acid