Tianjin Institute of Urology & Department of Urology, Second Hospital, Tianjin Medical University, Tianjin, China.
PLoS One. 2013 Jul 16;8(7):e68982. doi: 10.1371/journal.pone.0068982. Print 2013.
MicroRNAs, non-coding 20-22 nucleotide single-stranded RNAs, result in translational repression or degradation and gene silencing of their target genes, and significantly contribute to the regulation of gene expression. In the current study, we report that miR-182 expression was significantly upregulated in prostate cancer tissues and four cell lines, compared to benign prostatic hyperplasia tissues and normal prostatic epithelial (RWPE-1) cells. Ectopic overexpression of miR-182 significantly promotes the proliferation, increases the invasion, promotes the G1/S cell cycle transition and reduces early apotosis of PC-3 cells, while suppression of miR-182 decreased the proliferation and invasion, inhibits the G1/S cell cycle transition and increase early apotosis of PC-3 cells. Additionally, we demonstrated that miR-182 could downregulate expression of NDRG1 by directly targeting the NDRG1 3'-untranslated region. In conclusion, our results suggest that miR-182 plays an important role in the proliferation of human prostate cancer cells by directly suppressing the tumor supressor gene NDRG1. We uncovered a new epigenetic regulation of NDRG1.
微小 RNA（miRNA）是一类长约 20-22 个核苷酸的非编码单链 RNA，通过翻译抑制或降解以及靶基因的基因沉默来调节基因表达。在本研究中，我们报告称，与良性前列腺增生组织和正常前列腺上皮细胞（RWPE-1）相比，前列腺癌组织和四种细胞系中 miR-182 的表达显著上调。miR-182 的异位过表达可显著促进 PC-3 细胞的增殖，增加其侵袭性，促进 G1/S 细胞周期转换，并减少早期细胞凋亡，而抑制 miR-182 的表达则降低了 PC-3 细胞的增殖和侵袭性，抑制了 G1/S 细胞周期转换，并增加了早期细胞凋亡。此外，我们还证实 miR-182 可以通过直接靶向 NDRG1 的 3'非翻译区下调 NDRG1 的表达。总之，我们的研究结果表明，miR-182 通过直接抑制肿瘤抑制基因 NDRG1 在人前列腺癌细胞的增殖中发挥重要作用。我们揭示了 NDRG1 的一种新的表观遗传调控机制。
