Open AccessMiR ‐383 is Downregulated in Medulloblastoma and Targets Peroxiredoxin 3 ( PRDX3 )
Author(s) -
Li Kay KaWai,
Pang Jesse ChungSean,
Lau KinMang,
Zhou Liangfu,
Mao Ying,
Wang Yin,
Poon WaiSang,
Ng HoKeung
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12014
Subject(s) - microrna , peroxiredoxin , microbiology and biotechnology , biology , carcinogenesis , downregulation and upregulation , ectopic expression , western blot , transfection , reverse transcription polymerase chain reaction , chemistry , cell culture , gene expression , gene , genetics , biochemistry , peroxidase , enzyme
Accumulating evidence suggests that micro RNAs ( 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‐expresssed 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 .