microRNA 338-3p exhibits tumor suppressor role and its down-regulation is associated with adverse clinical outcome in prostate cancer patients
Bakkar A.; Alshalalfa M.; Petersen L.F.; Abou-Ouf H.; Al-Mami A.; Hegazy S.A.; Feng F.; Alhajj R.; Bijian K.; Alaoui-Jamali M.A.; Bismar T.A.
Date issued:
2016
Publisher:
Springer Netherlands
Series Info:
Molecular Biology Reports
43
Type:
Article
Keywords:
CXCR axis
,
ERG gene rearrangements
,
Invasion
,
MiR338-3p
,
Prognosis
,
Prostate cancer
,
chemokine receptor CXCR4
,
chemokine receptor CXCR7
,
microRNA
,
microRNA 338 3p
,
stromal cell derived factor 1
,
unclassified drug
,
chemokine receptor CXCR
,
chemokine receptor CXCR4
,
CXCL12 protein, human
,
CXCR4 protein, human
,
CXCR7 protein, human
,
microRNA
,
MIRN338 microRNA, human
,
stromal cell derived factor 1
,
adverse outcome
,
animal experiment
,
animal model
,
animal tissue
,
Article
,
cancer inhibition
,
cancer localization
,
cancer recurrence
,
cell invasion
,
cell viability
,
cohort analysis
,
controlled study
,
CXCL12 gene
,
CXCR4 gene
,
CXCR7 gene
,
down regulation
,
gene expression profiling
,
gene expression regulation
,
gene identification
,
gene overexpression
,
gene rearrangement
,
genetic association
,
human
,
human cell
,
in vitro study
,
in vivo study
,
male
,
microarray analysis
,
mouse
,
nonhuman
,
prostate cancer
,
prostate cancer cell line
,
signal transduction
,
stable expression
,
tumor volume
,
animal
,
gene expression regulation
,
genetics
,
metabolism
,
metastasis
,
pathology
,
prognosis
,
Prostatic Neoplasms
,
SCID mouse
,
tumor cell line
,
tumor suppressor gene
,
Animals
,
Cell Line, Tumor
,
Chemokine CXCL12
,
Gene Expression Regulation, Neoplastic
,
Genes, Tumor Suppressor
,
Humans
,
Male
,
Mice
,
Mice, SCID
,
MicroRNAs
,
Neoplasm Metastasis
,
Prognosis
,
Prostatic Neoplasms
,
Receptors, CXCR
,
Receptors, CXCR4
Abstract:
MicroRNAs (miRNAs) are small non-coding RNAs that function in transcriptional and post-transcriptional regulation of gene expression. Several miRNAs have been implicated in regulating prostate cancer (PCa) progression. Deregulations of miRNA regulatory networks have been reported in ERG positive PCa, which accounts for ~50�% of PCa and have been suggested to affect tumor aggressiveness. The function of miR338-3p, its prognostic significance, and its association with ERG positive PCa has not been fully investigated. Using microarray expression profiling, we identified miRNA338-3p as among the top deregulated miRNAs associated with ERG status in PCa. We investigated miR338-3p function using in vitro and in vivo experimental models and its expression was assessed and validated in clinical samples and a public cohort of localized and metastatic prostate cancer. miR338-3p was significantly down-regulated with disease progression from benign prostate tissue to primary and metastatic lesions. In localized disease, patients with lower miR338-3p expression levels showed increased association to biochemical recurrence and several adverse pathological parameters compared to patients with higher miRNA338-3p tissue expression levels. Using in vitro PCa cell models, overexpression of miR338-3p resulted in a decrease in cell invasion and expression of chemokine signalling genes CXCL12, CXCR4, and CXCR7. In vivo, orthotropic implantation of PC3 cells stably expressing miR338-3p was associated with a significant decrease in tumor weights compared to control cells. miR338-3p has anti-proliferative and anti-invasive properties. It affects CXCR4 axis, and its down-regulation is associated with adverse clinical outcomes in PCa patients. � 2016, Springer Science+Business Media Dordrecht.
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