title: MiR-22 is frequently downregulated in medulloblastomas and inhibits cell proliferation via the novel target PAPST1.
abstract: Medulloblastoma is the most frequent malignant central nervous system tumor in children. MicroRNAs (miRs) are small, non-coding RNAs that target protein-coding and non-coding RNAs, and play roles in a variety of cellular processes through regulation of multiple targets. In the present study, we analyzed miR-22 expression and its effect in cell proliferation and apoptosis in medulloblastomas. Quantitative reverse transcription PCR (RT-PCR) revealed significantly lower expression of miR-22 in 19 out of 27 (70%) medulloblastomas, D341, DAOY, ONS-76 medulloblastoma cell lines, compared with normal cerebellum. Forced expression of miR-22 by lentiviral vector transfection reduced cell proliferation and induced apoptosis, while knockdown of miR-22 increased proliferative activity in DAOY and ONS-76 cells. DAOY cells with miR-22 overexpression in nude mice yielded tumors smaller than those originated from control DAOY cells. Microarray analysis in DAOY cells with forced miR-22 expression showed significant changes in expression profiles, PAPST1 being the most significantly (10 folds) downregulated gene. Quantitative RT-PCR revealed PAPST1 mRNA upregulation in 18 out of 27 (67%) medulloblastomas. In addition, a luciferase reporter assay in ONS-76 and DAOY cells suggested that miR-22 directly targets the PAPST1 gene, and lentivirus-mediated knockdown of PAPST1 suppressed proliferation of DAOY and ONS-76 medulloblastoma cells. These results suggest that frequently downregulated miR-22 expression is associated with cell proliferation in medulloblastomas, and this may be at least in part via PAPST1, which is a novel target of miR-22.
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qing-Fu
authors.initials: QF
authors.lastname: Xu
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Pan
authors.forename: Li-Chao
authors.initials: LC
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.forename: Qi-Lin
authors.initials: QL
authors.lastname: Huang
authors.forename: Jesse Chung-Sean
authors.initials: JC
authors.lastname: Pang
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
authors.forename: Sheng-Qing
authors.initials: SQ
authors.lastname: Lv
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D002528:Cerebellar Neoplasms / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D006801:Humans; D007223:Infant; D008527:Medulloblastoma / Q000503:physiopathology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D027321:Anion Transport Proteins; C548375:MIRN22 microRNA, human; D026901:Membrane Transport Proteins; D035683:MicroRNAs; C547745:PAPST1 protein, mouse; C476248:SLC35B2 protein, human; D000076988:Sulfate Transporters
keywords: PAPST1; apoptosis; cell proliferation; medulloblastoma; miR-22