title: Downregulation of miR-137 and miR-6500-3p promotes cell proliferation in pediatric high-grade gliomas.
abstract: Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors affecting children, and outcomes have remained dismal, even with access to new multimodal therapies. In this study, we compared the miRNomes and transcriptomes of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p as significantly downregulated in pHGGs. miR-137 or miR-6500-3p overexpression reduced cell proliferation in two pHGG cell lines, SF188 and UW479. CENPE, KIF14 and NCAPG levels were significantly higher in pHGGs than pLGGs, and were direct targets of miR-137 or miR-6500-3p. Furthermore, knockdown of CENPE, KIF14 or NCAPG combined with temozolomide treatment resulted in a combined suppressive effect on pHGG cell proliferation. In summary, our results identify novel mRNA/miRNA interactions that contribute to pediatric glioma malignancy and represent potential targets for the development of new therapeutic strategies.
authors.affiliation: Institutes of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Muh-Lii
authors.initials: ML
authors.lastname: Liang
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|Comprehensive Cancer Center of Taipei Medical University, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Hsieh
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kim-Hai
authors.initials: KH
authors.lastname: Ng
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Fong
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Institutes of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Meng-En
authors.initials: ME
authors.lastname: Chao
authors.affiliation: Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Da-Jung
authors.initials: DJ
authors.lastname: Liu
authors.affiliation: Institutes of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shing-Shiung
authors.initials: SS
authors.lastname: Chu
authors.affiliation: Institutes of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wan
authors.initials: W
authors.lastname: Chen
authors.affiliation: Comprehensive Cancer Center of Taipei Medical University, Taipei Medical University, Taipei, Taiwan.|Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Liu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|National PET/Cyclotron Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Molecular and Genetic Imaging Core/Taiwan Mouse Clinic National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan.
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Donald Ming-Tak
authors.initials: DM
authors.lastname: Ho
authors.affiliation: Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.|Institutes of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.|Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tai-Tong
authors.initials: TT
authors.lastname: Wong
authors.affiliation: Institutes of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Cancer Research Center & Genome Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Immunity and Inflammation Research Center, National Yang-Ming University, Taipei, Taiwan.|Genomic Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Institutes of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.|Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.|Cancer Research Center & Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D015513:Oncogene Proteins / Q000235:genetics; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C545567:MIRN137 microRNA, human; C000625046:MIRN6500 microRNA, human; D035683:MicroRNAs; C533611:NCAPG protein, human; D015513:Oncogene Proteins; C068688:centromere protein E; D003606:Dacarbazine; C502598:KIF14 protein, human; D016547:Kinesins; D000077204:Temozolomide
keywords: CENPE; KIF14; NCAPG; miR-137; miR-6500-3p