The functional significance of microRNA-145 in prostate cancer.
BACKGROUND
MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in numerous cellular processes. Recent studies have shown aberrant expression of miRNAs in prostate cancer tissues and cell lines. On the basis of miRNA microarray data, we found that miR-145 is significantly downregulated in prostate cancer.


RESULTS
We investigated the expression and functional significance of miR-145 in prostate cancer. The expression of miR-145 was low in all the prostate cell lines tested (PC3, LNCaP and DU145) compared with the normal cell line, PWR-1E, and in cancerous regions of human prostate tissue when compared with the matched adjacent normal. Overexpression of miR-145 in PC3-transfected cells resulted in increased apoptosis and an increase in cells in the G2/M phase, as detected by flow cytometry. Investigation of the mechanisms of inactivation of miR-145 through epigenetic pathways revealed significant DNA methylation of the miR-145 promoter region in prostate cancer cell lines. Microarray analyses of miR-145-overexpressing PC3 cells showed upregulation of the pro-apoptotic gene TNFSF10, which was confirmed by real-time PCR and western analysis.


CONCLUSIONS
One of the genes significantly upregulated by miR-145 overexpression is the proapoptotic gene TNFSF10. Therefore, modulation of miR-145 may be an important therapeutic approach for the management of prostate cancer.
Zaman
M S
MS
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA, USA.
Chen
Y
Y
Deng
G
G
Shahryari
V
V
Suh
S O
SO
Saini
S
S
Majid
S
S
Liu
J
J
Khatri
G
G
Tanaka
Y
Y
Dahiya
R
R
D017209:Apoptosis; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D015536:Down-Regulation; D020868:Gene Silencing; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D046228:Microarray Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D015854:Up-Regulation
D006877:Hydroxamic Acids; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C012589:trichostatin A; D000077209:Decitabine; D019833:Genistein; D001374:Azacitidine