title: Involvement of parental imprinting in the antisense regulation of onco-miR-372-373.
abstract: The monoallelic nature of imprinted genes renders them highly susceptible to genetic and epigenetic perturbations, potentially resulting in transformation and disease. Here we show, using parthenogenetic induced pluripotent stem cells, an imprinted transcript that serves as an antisense regulator of onco-miR-372-3 (named anti-miR-371-3). As miR-372-3 have been shown to have an oncogenic role in testicular germ cell tumours, we study the involvement of their antisense transcript in these cells. Our results suggest that hypermethylation, leading to loss-of-expression of the imprinted antisense transcript, contributes to tumorigenic transformation by affecting the downstream target LATS2. Finally, we provide evidence for a tumour suppressive role of anti-miR-371-3, as its overexpression in tumour cells results in cell growth arrest and apoptosis, and prevents tumour formation on injection into immunodeficient mice.
authors.affiliation: Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Stelzer
authors.forename: Ido
authors.initials: I
authors.lastname: Sagi
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D019175:DNA Methylation; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C554834:MIRN371 microRNA, human; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; C522633:LATS2 protein, mouse; D017346:Protein Serine-Threonine Kinases