Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland.
Masovian Specialist Hospital in Ostroleka, Ostroleka, Poland.
Cancer Lett. 2018 Jan 1;412:155-169. doi: 10.1016/j.canlet.2017.10.019. Epub 2017 Oct 25.
In our previous study we found altered expression of 19 adhesion-related genes in renal tumors. In this study we hypothesized that disturbed expression of adhesion-related genes could be caused by microRNAs: short, non-coding RNAs that regulate gene expression. Here, we found that expression of 24 microRNAs predicted to target adhesion-related genes was disturbed in renal tumors and correlated with expression of their predicted targets. miR-25-3p, miR-30a-5p, miR-328 and miR-363-3p directly targeted adhesion-related genes, including COL5A1, COL11A1, ITGA5, MMP16 and THBS2. miR-363-3p and miR-328 inhibited proliferation of renal cancer cells, while miR-25-3p inhibited adhesion, promoted proliferation and migration of renal cancer cells. TGF-β1 influenced the expression of miR-25-3p, miR-30a-5p, and miR-328. The analyzed microRNAs, their target genes and TGF-β1 formed a network of strong correlations in tissue samples from renal cancer patients. The expression signature of microRNAs linked with TGF-β1 levels correlated with poor survival of renal cancer patients. The results of our study suggest that TGF-β1 coordinates the expression of microRNA network that regulates cellular adhesion in cancer.
在我们之前的研究中，我们发现肾脏肿瘤中 19 个黏附相关基因的表达发生了改变。在本研究中，我们假设黏附相关基因表达的紊乱可能是由 microRNAs 引起的：microRNAs 是一种短的、非编码的 RNA，可以调节基因表达。在这里，我们发现 24 个 microRNAs 的表达被预测可以靶向黏附相关基因，并且与它们预测的靶基因的表达相关。miR-25-3p、miR-30a-5p、miR-328 和 miR-363-3p 直接靶向黏附相关基因，包括 COL5A1、COL11A1、ITGA5、MMP16 和 THBS2。miR-363-3p 和 miR-328 抑制肾癌细胞的增殖，而 miR-25-3p 抑制肾癌细胞的黏附，促进增殖和迁移。TGF-β1 影响 miR-25-3p、miR-30a-5p 和 miR-328 的表达。在肾癌细胞患者的组织样本中，分析的 microRNAs、它们的靶基因和 TGF-β1 形成了一个具有强相关性的网络。与 TGF-β1 水平相关的 microRNAs 的表达特征与肾癌细胞患者的不良生存相关。我们的研究结果表明，TGF-β1 协调了 microRNA 网络的表达，该网络调节了癌症中的细胞黏附。
