Experiment Detail



Experiment IDEXP00212
ReferenceTitle: Epigenetic repression of miR-31 disrupts androgen receptor homeostasis andcontributes to prostate cancer progression.
Author: Lin PC, Chiu YL, Banerjee S, Park K, Mosquera JM, Giannopoulou E, Alves P,Tewari AK, Gerstein MB, Beltran H, Melnick AM, Elemento O, Demichelis F, RubinMA.
Journal: Cancer Res. 2013 Feb 1;73(3):1232-44. doi: 10.1158/0008-5472.CAN-12-2968. Epub2012 Dec 11.
Abstract: Androgen receptor signaling plays a critical role in prostate cancerpathogenesis. Yet, the regulation of androgen receptor signaling remains elusive.Even with stringent androgen deprivation therapy, androgen receptor signalingpersists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31, and androgen receptorsignaling. We examined primary and metastatic prostate cancer and found thatmiR-31 expression was reduced as a result of promoter hypermethylation, andimportantly, the levels of miR-31 expression were inversely correlated with theaggressiveness of the disease. As the expression of androgen receptor and miR-31 was inversely correlated in the cell lines, our study further suggested thatmiR-31 and androgen receptor could mutually repress each other. Upregulation ofmiR-31 effectively suppressed androgen receptor expression through multiplemechanisms and inhibited prostate cancer growth in vivo. Notably, we found thatmiR-31 targeted androgen receptor directly at a site located in the codingregion, which was commonly mutated in prostate cancer. In addition, miR-31suppressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2.Together, our findings suggest a novel androgen receptor regulatory mechanismmediated through miR-31 expression. The downregulation of miR-31 may disruptcellular homeostasis and contribute to the evolution and progression of prostate cancer. We provide implications for epigenetic treatment and support clinicaldevelopment of detecting miR-31 promoter methylation as a novel biomarker.
PMID: 23233736
Expressiion ProfileDescription: microRNA profiling in paired human prostate cancer and benign prostate tissue
Organism: Homo sapiens
GEO ID: GSE36802
Platform: GPL8786
Number of samples: 42
Design and SampleCancer Type: prostate cancer
Cancer SubType: N/D
Cell Line: N/D
Experimental Design: cancer vs normal
Case Sample: prostate tumour
Control Sample: normal prostate
Num of Case: 21
Num of Control: 21
Quantification Software: Limma
Num of miRNAs: 597
IdentificationNum of Up: 39
Num of Down: 28