Chung Yueh-Hua, Li Sung-Chou, Kao Ying-Hsien, Luo Hao-Lun, Cheng Yuan-Tso, Lin Pey-Ru, Tai Ming-Hong, Chiang Po-Hui
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Int J Mol Sci. 2017 Aug 22;18(8):1826. doi: 10.3390/ijms18081826.
The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions.
We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy. The miRNAs signatures of three selected UTUC samples using next-generation sequencing showed that miR-30a-5p was significantly downregulated in UTUC tumors compared to adjacent normal tissues. The differentially-expressed miRNAs were specifically validated by quantitative real-time polymerase chain reaction. In addition, the miRNA expression signatures were analyzed with the transcriptome profile characterized by microarray. Further in vitro studies indicated that overexpression of miR-30a-5p significantly suppressed proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in cultured BFTC-909 UTUC cells As a potential target gene of miR-30a-5p in the tight junction pathway suggested by the pathway enrichment analysis, the reduced expression of tight junction protein claudin-5 in UTUC cells was demonstrated to be upregulated by miR-30a-5p genetic delivery.
Taken together, our findings demonstrated that miR-30a-5p inhibits proliferation, metastasis, and EMT, and upregulates the expression of tight junction claudin-5 in UTUC cells. Thus, miR-30a-5p may provide a promising therapeutic strategy for UTUC treatment.
微小RNA(miRNA)参与癌症发展及其作为预后生物标志物的潜力日益为人所知。然而,miRNA的特征及其在上尿路尿路上皮癌(UTUC)肿瘤发生中的调控作用仍有待阐明。本研究旨在分析UTUC肿瘤组织中的miRNA表达模式,并鉴定具有预后和/或治疗功能的候选miRNA。
我们收集了22例接受肾输尿管切除术患者的UTUC组织和相邻正常组织样本。使用下一代测序对三个选定的UTUC样本进行miRNA特征分析,结果显示与相邻正常组织相比,miR-30a-5p在UTUC肿瘤中显著下调。通过定量实时聚合酶链反应对差异表达的miRNA进行了特异性验证。此外,利用微阵列表征的转录组图谱分析了miRNA表达特征。进一步的体外研究表明,miR-30a-5p的过表达显著抑制了培养的BFTC-909 UTUC细胞的增殖、迁移和上皮-间质转化(EMT)。通路富集分析提示紧密连接通路中miR-30a-5p的潜在靶基因,通过miR-30a-5p基因传递证实UTUC细胞中紧密连接蛋白claudin-5的表达降低得到上调。
综上所述,我们的研究结果表明miR-30a-5p抑制UTUC细胞的增殖、转移和EMT,并上调紧密连接claudin-5的表达。因此,miR-30a-5p可能为UTUC治疗提供一种有前景的治疗策略。