miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer.
miRNAs have proven to be key regulators of gene expression and are differentially expressed in various diseases, including cancer. Our aim was to identify epigenetically dysregulated genes in prostate cancer. We performed miRNA expression profiling after relieving epigenetic modifications in 6 prostate cancer cell lines and nonmalignant prostate epithelial cells. Thirty-eight miRNAs showed increased expression in any prostate cancer cell line after 5-aza-2'-deoxycytidine (5azadC) and trichostatin A (TSA) treatments. Six of these also had decreased expression in clinical prostate cancer samples compared to benign prostatic hyperplasia. Among these, miR-193b was methylated in 22Rv1 cell line at a CpG island approximately 1 kb upstream of the miRNA locus. Expressing miR-193b in 22Rv1 cells using pre-miR-193b oligonucleotides caused a significant growth reduction (p < 0.001) resulting from a decrease of cells in S-phase of the cell cycle (p < 0.01). In addition, the anchorage independent growth was partially inhibited in transiently miR-193b-expressing 22Rv1 cells (p < 0.01). Altogether, our data suggest that miR-193b is an epigenetically silenced putative tumor suppressor in prostate cancer.
Rauhala
Hanna E
HE
Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Jalava
Sanni E
SE
Isotalo
Jarkko
J
Bracken
Hazel
H
Lehmusvaara
Saara
S
Tammela
Teuvo L J
TL
Oja
Hannu
H
Visakorpi
Tapio
T
D001483:Base Sequence; D002453:Cell Cycle; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
C546818:MIRN193 microRNA, human; D035683:MicroRNAs