PRDM1 is directly targeted by miR-30a-5p and modulates the Wnt/β-catenin pathway in a Dkk1-dependent manner during glioma growth.
The transcriptional regulator PRDM1 controls cell-fate decisions and has been implicated in human tumorigenesis as a tumor suppressor. However, its pathological role in glioma remains elusive. In this study, we showed that PRDM1 protein levels were inversely correlated with the pathological grade of gliomas and were predictive of patient survival in a retrospective analysis. Restored expression of PRDM1 inhibited proliferation and suppressed invasion by glioma cells. Mechanistic investigation revealed that PRDM1 attenuated glioma malignancy by negatively modulating Wnt/β-catenin signaling and this modulation was dependent on the Wnt inhibitor Dkk1. Using bioinformatics and biological approaches, we found that PRDM1 was a direct target of miR-30a-5p, and PRDM1 dysfunction was attributable to miR-30a-5p-mediated repression. Our results provide evidence that PRDM1 deficiency contributes to the phenotype maintenance and pathogenesis of gliomas.
Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Xuan
X
Wang
Kun
K
Wang
Lei
L
Han
Anling
A
Zhang
Zhendong
Z
Shi
Kailiang
K
Zhang
Hongwei
H
Zhang
Shaohua
S
Yang
Peiyu
P
Pu
Changhong
C
Shen
Chunjiang
C
Yu
Chunsheng
C
Kang
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1