Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Int J Cancer. 2010 Sep 1;127(6):1363-72. doi: 10.1002/ijc.25162.
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.
miRNAs 已被证明是基因表达的关键调节剂,在包括癌症在内的各种疾病中表达不同。我们的目的是确定前列腺癌中表观遗传失调的基因。我们在 6 种前列腺癌细胞系和非恶性前列腺上皮细胞中解除表观遗传修饰后,进行了 miRNA 表达谱分析。在 5-氮杂-2'-脱氧胞苷(5azadC)和曲古抑菌素 A(TSA)处理后,38 种 miRNA 在任何前列腺癌细胞系中的表达均增加。其中 6 种 miRNA 在与良性前列腺增生相比的临床前列腺癌样本中表达降低。在这些 miRNA 中,miR-193b 在 22Rv1 细胞系中在 miRNA 基因座上游约 1 kb 的 CpG 岛上发生甲基化。使用 pre-miR-193b 寡核苷酸在 22Rv1 细胞中表达 miR-193b 导致细胞周期 S 期的细胞数量减少(p < 0.01),从而导致细胞生长显著减少(p < 0.001)。此外,瞬时表达 miR-193b 的 22Rv1 细胞的无锚定独立生长部分受到抑制(p < 0.01)。总之,我们的数据表明,miR-193b 是前列腺癌中一种表观遗传沉默的潜在肿瘤抑制因子。