MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer.
BACKGROUND
MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of approximately 60% of all human genes. They play important roles in numerous cellular processes, including development, proliferation, and apoptosis. Currently, it is believed that miRNAs elicit their effect by silencing the expression of target genes. In this study, the authors demonstrated that miRNA-205 (miR-205) induced the expression the interleukin (IL) tumor suppressor genes IL24 and IL32 by targeting specific sites in their promoters.


METHODS
The methods used in this study included transfection of small RNAs; quantitative real-time polymerase chain reaction; in situ hybridization; fluorescence-labeled in situ hybridization; cell cycle, apoptosis, cell viability, migratory, clonability, and invasion assays; immunoblotting; and luciferase reporter, nuclear run-on, and chromatin immunoprecipitation assays.


RESULTS
The results revealed that miR-205 was silenced in prostate cancer. Its re-expression induced apoptosis and cell cycle arrest. It also impaired cell growth, migration, clonability, and invasiveness of prostate cancer cells. Micro-RNA-205 induced the expression of tumor suppressor genes IL24 and IL32 at both the messenger RNA and protein levels. The induction of in vitro transcription and enrichment of markers for transcriptionally active promoters in the IL24 and IL32 genes was observed in response to miR-205.


CONCLUSIONS
In this study, a new function for miR-205 was identified that specifically activated tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a newly identified function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (eg, IL24, IL32) or other dysregulated genes by miRNA may contribute to a novel therapeutic approach for the treatment of prostate cancer.
Majid
Shahana
S
Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California, USA.
Dar
Altaf A
AA
Saini
Sharanjot
S
Yamamura
Soichiro
S
Hirata
Hiroshi
H
Tanaka
Yuichiro
Y
Deng
Guoren
G
Dahiya
Rajvir
R
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D015533:Transcriptional Activation; D000099180:Interleukin-24
D007378:Interleukins; D035683:MicroRNAs; D000099180:Interleukin-24; C496971:IL32 protein, human; C534425:MIR205, human