title: miR-367 promotes proliferation and stem-like traits in medulloblastoma cells.
abstract: In medulloblastoma, abnormal expression of pluripotency factors such as LIN28 and OCT4 has been correlated with poor patient survival. The miR-302/367 cluster has also been shown to control self-renewal and pluripotency in human embryonic stem cells and induced pluripotent stem cells, but there is limited, mostly correlational, information about these pluripotency-related miRNA in cancer. We evaluated whether aberrant expression of such miRNA could affect tumor cell behavior and stem-like traits, thereby contributing to the aggressiveness of medulloblastoma cells. Basal expression of primary and mature forms of miR-367 were detected in four human medulloblastoma cell lines and expression of the latter was found to be upregulated upon enforced expression of OCT4A. Transient overexpression of miR-367 significantly enhanced tumor features typically correlated with poor prognosis; namely, cell proliferation, 3-D tumor spheroid cell invasion and the ability to generate neurosphere-like structures enriched in CD133 expressing cells. A concurrent downregulation of the miR-367 cancer-related targets RYR3, ITGAV and RAB23, was also detected in miR-367-overexpressing cells. Overall, these findings support the pro-oncogenic activity of miR-367 in medulloblastoma and reveal a possible mechanism contributing to tumor aggressiveness, which could be further explored to improve patient stratification and treatment of this important type of pediatric brain cancer.
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Carolini
authors.initials: C
authors.lastname: Kaid
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Patrícia B G
authors.initials: PB
authors.lastname: Silva
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Beatriz A
authors.initials: BA
authors.lastname: Cortez
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Rodini
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Semedo-Kuriki
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil.
authors.forename: Oswaldo K
authors.initials: OK
authors.lastname: Okamoto
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D010455:Peptides / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D018874:Spheroids, Cellular / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C568081:MIRN367 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D019837:Ryanodine Receptor Calcium Release Channel; C486614:RAB23 protein, human; D020691:rab GTP-Binding Proteins
keywords: Cancer stem cell; medulloblastoma; miR-367; microRNA; pluripotency