title: MIR-137 suppresses growth and invasion, is downregulated in oligodendroglial tumors and targets CSE1L.
abstract: MicroRNA-137 (miR-137) expression has been reported to be decreased in astrocytic tumors in two expression profiling studies but its role in the pathogenesis of oligodendroglial tumors is still limited. In this study, we demonstrate that miR-137 expression is significantly downregulated in a cohort of 35 oligodendroglial tumors and nine glioma cell lines compared with normal brains. Lower miR-137 expression is associated with shorter progressive-free survival and overall survival. Restoration of miR-137 expression in an oligodendroglial cells TC620, and also glioblastoma cells of U87 and U373 significantly suppressed cell growth, anchorage-independent growth, as well as invasion. Demethylation and deacetylation treatments resulted in upregulation of miR-137 expression in TC620 cells. In silico analysis showed that CSE1 chromosome segregation 1-like (yeast) (CSE1L) is a potential target gene of miR-137. Luciferase reporter assay demonstrated that miR-137 negatively regulates CSE1L by interaction between miR-137 and complementary sequences in the 3' UTR of CSE1L. Immunohistochemistry revealed that CSE1L is upregulated in oligodendroglial tumors. Knockdown of CSE1L resulted in similar outcomes as overexpressing miR-137 in oligodendroglioma cells and glioblastoma cells. Overall, our data suggest that miR-137 regulates growth of glioma cells and targets CSE1L, providing further understanding in the tumorigenesis of gliomas.
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Jesse Chung-Sean
authors.initials: JC
authors.lastname: Pang
authors.forename: Aden Ka-Yin
authors.initials: AK
authors.lastname: Chan
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Kin-Mang
authors.initials: KM
authors.lastname: Lau
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shi
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D029563:Cellular Apoptosis Susceptibility Protein / Q000235:genetics / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D003094:Collagen; D000077209:Decitabine; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053208:Kaplan-Meier Estimate; D007797:Laminin; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009837:Oligodendroglioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011509:Proteoglycans
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007797:Laminin; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D011509:Proteoglycans; C059485:matrigel; C012589:trichostatin A; D000077209:Decitabine; D003094:Collagen; D001973:Bromodeoxyuridine; D001374:Azacitidine