Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma.
MicroRNAs are small noncoding 18- to 24-nt RNAs that are predicted to regulate expression of as many as 30% of protein-encoding genes. In prostate adenocarcinoma, 39 microRNAs are up-regulated, and six microRNAs are down-regulated. Production and function of microRNA requires coordinated processing by proteins of the microRNA machinery. Dicer, an RNase III endonuclease, is an essential component of the microRNA machinery. From a gene array analysis of 16 normal prostate tissue samples, 64 organ-confined, and four metastatic prostate adenocarcinomas, we identified an up-regulation of major components of the microRNA machinery, including Dicer, in metastatic prostate adenocarcinoma. Immunohistochemical studies on a tissue microarray consisting of 232 prostate specimens confirmed up-regulation of Dicer in prostatic intraepithelial neoplasia and in 81% of prostate adenocarcinoma. The increased Dicer level in prostate adenocarcinoma correlated with clinical stage, lymph node status, and Gleason score. Western blot analysis of benign and neoplastic prostate cell lines further confirmed Dicer up-regulation in prostate adenocarcinoma. Dicer up-regulation may explain an almost global increase of microRNA expression in prostate adenocarcinoma. The presence of up-regulated microRNA machinery may predict the susceptibility of prostate adenocarcinoma to RNA interference-based therapy.
Chiosea
Simion
S
Department of Pathology, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian, C920.1, 200 Lothrop St., Pittsburgh, PA 15213, USA. chioseasi@upmc.edu
Jelezcova
Elena
E
Chandran
Uma
U
Acquafondata
Marie
M
McHale
Teresa
T
Sobol
Robert W
RW
Dhir
Rajiv
R
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D004722:Endoribonucleases / Q000276:immunology / Q000378:metabolism*; D004848:Epithelium / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D011467:Prostate / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D043244:Ribonuclease III; D015854:Up-Regulation
D035683:MicroRNAs; D004722:Endoribonucleases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases