title: MiR-383 is downregulated in medulloblastoma and targets peroxiredoxin 3 (PRDX3).
abstract: Accumulating evidence suggests that microRNAs (miRNAs) are over- or under-expressed in tumors, and abnormalities in miRNA expression may contribute to carcinogenesis. MiR-383 was previously identified as one of the under-expressed miRNAs in medulloblastoma (MB) by miRNA expression profiling. Quantitative reverse transcription polymerase chain reaction (RT-PCR)-based miRNA assays showed an enrichment of miR-383 in normal brain. Based on these data, we speculated that miR-383 is important in MB pathogenesis. In this study, we demonstrated significant downregulation of miR-383 in 23/29 (79%) MB samples and 7/7 (100%) MB cells lines. Ectopic expression of miR-383 in MB cells led to suppression of cell growth, cell accumulation at sub-G1 phase and alteration of apoptosis-related proteins. By transcriptomic analysis and computational algorithms, we identified peroxiredoxin 3 (PRDX3) as a target gene of miR-383. Luciferase reporter assay confirmed that miR-383 negatively regulated PRDX3 by interaction between miR-383 and complementary sequences in the 3' UTR of PRDX3. MiR-383 repressed PRDX3 at transcriptional and translational levels as revealed by quantitative RT-PCR and Western blot analysis. Furthermore, depletion of PRDX3 by siRNAs resulted in similar effects as observed in miR-383-transfected cells. In conclusion, miR-383 acts as a regulator controlling cell growth of MB, at least in part, through targeting PRDX3.
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: Jesse Chung-Sean
authors.initials: JC
authors.lastname: Pang
authors.forename: Kin-Mang
authors.initials: KM
authors.lastname: Lau
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: Wai-Sang
authors.initials: WS
authors.lastname: Poon
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D002528:Cerebellar Neoplasms / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D000077209:Decitabine; D015536:Down-Regulation / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D061105:Peroxiredoxin III / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C558685:MIRN383 microRNA, human; D035683:MicroRNAs; C012589:trichostatin A; D000077209:Decitabine; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D001374:Azacitidine