miR-105 inhibits prostate tumour growth by suppressing CDK6 levels.
miR-105 inhibits prostate tumour growth by suppressing CDK6 levels.
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DOI：
10.1371/journal.pone.0070515
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Addison CL
中科院分区：
文献类型：
--
作者：
Honeywell DR;Cabrita MA;Zhao H;Dimitroulakos J;Addison CL
最近，微小(MI)RNA在肿瘤基因表达调控中的重要作用已被证实。为了进一步了解miRNA在前列腺癌生长和发展中的作用，我们检测了两种侵袭性前列腺癌细胞系PC3和DU145中miRNA的表达，并将其与正常前列腺上皮细胞中的表达进行了比较。尽管有一些miRNAs是差异表达的，但我们的分析集中在miR-105上，这是一种以前没有与前列腺癌相关的新型miRNA。与正常前列腺上皮细胞相比，两种肿瘤细胞系的MIR-105水平均显著降低。为了确定miR-105在前列腺癌发病机制中的潜在作用，我们在PC3和DU145细胞中过表达miR-105，并确定了它对各种肿瘤发生特性的影响。MIR-105过表达抑制了肿瘤细胞的增殖，抑制了肿瘤在非锚定三维条件下的生长，抑制了肿瘤的体外侵袭，具有高侵袭性的肿瘤细胞的特性。在使用这些细胞系的异种移植模型中，miR-105的过表达抑制了体内肿瘤的生长，这具有潜在的临床意义。我们进一步确定CDK6是miR-105的假定靶点，这可能是我们检测中观察到的抑制肿瘤细胞生长的主要贡献因素。我们的结果表明，miR-105抑制肿瘤细胞的增殖，因此可能是一种新的治疗相关的细胞靶点，以抑制前列腺癌患者的肿瘤生长或侵袭性肿瘤的标志。
A significant role for micro (mi)RNA in the regulation of gene expression in tumours has been recently established. In order to further understand how miRNA expression may contribute to prostate tumour growth and progression, we evaluated expression of miRNA in two invasive prostate tumour lines, PC3 and DU145, and compared it to that in normal prostate epithelial cells. Although a number of miRNAs were differentially expressed, we focused our analysis on miR-105, a novel miRNA not previously linked to prostate cancer. miR-105 levels were significantly decreased in both tumour cell lines in comparison to normal prostate epithelial cells. To determine its potential role in prostate cancer pathogenesis, we overexpressed miR-105 in both PC3 and DU145 cells and determined its effect on various tumourigenic properties. miR-105 overexpression inhibited tumour cell proliferation, tumour growth in anchorage-independent three-dimensional conditions and tumour invasion in vitro, properties of highly aggressive tumour cells. Of potential clinical significance, miR-105 overexpression inhibited tumour growth in vivo in xenograft models using these cell lines. We further identified CDK6 as a putative target of miR-105 which is likely a main contributor to the inhibition of tumour cell growth observed in our assays. Our results suggest that miR-105 inhibits tumour cell proliferation and hence may represent a novel therapeutically relevant cellular target to inhibit tumour growth or a marker of aggressive tumours in prostate cancer patients.
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