Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, Malmö, Sweden.
Int J Cancer. 2010 Dec 15;127(12):2768-76. doi: 10.1002/ijc.25269.
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer (PCa) and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in PCa (p = 0.0005) by performing qRT-PCR on 49 TURPs from PCa patients compared to 25 from patients with benign prostatic hyperplasia. The miR-34c expression was found to inversely correlate to aggressiveness of the tumor, WHO grade, PSA levels and occurrence of metastases. Furthermore, a Kaplan-Meier analysis of patient survival based on miR-34c expression levels divided into low (< 50th percentile) and high (> 50th percentile) expression, significantly divides the patients into high risk and low risk patients (p = 0.0003, log-rank test). The phenotypic effects of miR-34c deregulation were studied in prostate cell lines, where ectopic expression of miR-34c decreased cell growth, due to both a decrease in cellular proliferation rate and an increase in apoptosis. In concordance to this, miR-34c was found to negatively regulate the oncogenes E2F3 and BCL-2, which stimulates proliferation and suppress apoptosis in PCa cells, respectively. Reversely, we could also show that blocking miR-34c in vitro increases cell growth. Further, ectopic expression of miR-34c was found to suppress migration and invasion. Our findings provide new insight into the role of miR-34c in the prostate, exhibiting tumor suppressing effects on proliferation, apoptosis and invasiveness.
微小 RNA（miRNAs）是一种小的非编码 RNA，可在后转录水平上调节基因表达。已经有几项关于前列腺癌（PCa）中 miRNA 失调的报道，并且 miRNA 参与前列腺肿瘤发生的生物学证据正在增加。在这项研究中，我们通过对 49 例来自 PCa 患者的 TURP 与 25 例来自良性前列腺增生患者的 TURP 进行 qRT-PCR，显示 miR-34c 在 PCa 中下调（p=0.0005）。miR-34c 的表达与肿瘤的侵袭性、WHO 分级、PSA 水平和转移的发生呈负相关。此外，根据 miR-34c 表达水平分为低（<50 百分位）和高（>50 百分位）表达的患者生存 Kaplan-Meier 分析，显著将患者分为高危和低危患者（p=0.0003，对数秩检验）。在前列腺细胞系中研究了 miR-34c 失调的表型效应，其中 miR-34c 的异位表达由于细胞增殖率降低和细胞凋亡增加而降低细胞生长。与此一致，发现 miR-34c 负调节癌基因 E2F3 和 BCL-2，它们分别刺激 PCa 细胞的增殖和抑制凋亡。相反，我们还可以证明体外阻断 miR-34c 会增加细胞生长。此外，异位表达 miR-34c 可抑制迁移和侵袭。我们的研究结果提供了 miR-34c 在前列腺中的作用的新见解，其对增殖、凋亡和侵袭性具有肿瘤抑制作用。
