title: Deleting maternal Gtl2 leads to growth enhancement and decreased expression of stem cell markers in teratoma.
abstract: The distal region of mouse chromosome 12 harbors the Dlk1-Dio3 domain, is essential for normal development and encodes maternally expressed noncoding RNAs (ncRNAs), including Gtl2 as well as paternally expressed proteins.Gtl2 works as a tumor suppressor in several types of human cancer cell lines; however, whether this reflects its function in vivo is unknown. Deleting Gtl2 from the maternal allele (Gtl2((-/+))) results in loss of expression of Gtl2 and decreased expression of downstream ncRNAs, including many miRNAs. To determine the role of ncRNAs in tumorigenesis, we induced teratomas by engrafting E6.5 embryos (wildtype or Gtl2((-/+))) under the kidney capsule of scid mice. Some teratomas derived from the Gtl2((-/+)) embryos exhibited hypertrophic growth, suggesting that ncRNAs, including Gtl2, may act as tumor suppressors in vivo. Microarray analysis of miRNAs expressed by Gtl2((-/+)) teratomas revealed decreased expression of 28 miRNAs encoded by the Dlk1-Dio3 domain, low expression of embryonic stem cell-specific miRNAs and dysregulation of miRNAs involved in tumorigenesis. This study suggests that downregulation of ncRNAs in the Dlk1-Dio3 domain leads to enhanced teratoma growth and repression of stem cell markers.
authors.affiliation: Department of Bioscience, Tokyo University of Agriculture, Tokyo 156-0054, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takahashi
authors.forename: Eito
authors.initials: E
authors.lastname: Yamaguchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kono
mesh_terms: D016475:3T3 Cells; D000483:Alleles; D000818:Animals; D002135:Calcium-Binding Proteins; D049109:Cell Proliferation; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018392:Genomic Imprinting; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013724:Teratoma / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C422882:MEG3 non-coding RNA, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase