Yu Haifeng, Duan Ping, Zhu Haibo, Rao Dapang
Department of Urology, The Second Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
Department of Obstetric and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
Am J Transl Res. 2017 Mar 15;9(3):1213-1221. eCollection 2017.
Increasing evidence has suggested that microRNA (miRNA) dysregulation may contribute to tumor progression and metastasis. However, the role of miR-613 in bladder cancer was still unknown.
qRT-PCR and Western blotting were performed to detect the expression of miR-613 and its direct target gene. CCK-8 analysis, qRT-PCR and cell invasion were performed to measure the cell function.
We demonstrated that the expression of miR-613 was downregulated in the bladder cancer cell lines. In addition, miR-613 expression was downregulated in the bladder cancer tissues compared to the adjacent normal tissues. Out of 35 bladder cancer tissues, miR-613 was downregulated in 27 cases compared to the adjacent tissues. Ectopic expression of miR-613 suppressed the bladder cancer cell proliferation and invasion. Moreover, miR-613 overexpression enhanced the expression of epithelial biomarker, Ecadherin, and suppressed the expression of mesenchymal biomarker, Vimentin, Snail and N-cadherin. Furthermore, we identified the Sphingosine kinase 1 (SphK1) as the direct target gene of miR-613 in the bladder cancer cell. Restoration of Sphk1 partially rescued miR-613-inhibited bladder cancer cell proliferation, invasion and EMT.
These data suggested that miR-613 acted a tumor suppressive role in bladder cancer through targeting SphK1 in bladder.
越来越多的证据表明,微小RNA(miRNA)失调可能促进肿瘤进展和转移。然而,miR-613在膀胱癌中的作用仍不清楚。
采用qRT-PCR和蛋白质免疫印迹法检测miR-613及其直接靶基因的表达。进行CCK-8分析、qRT-PCR和细胞侵袭实验以检测细胞功能。
我们发现miR-613在膀胱癌细胞系中的表达下调。此外,与相邻正常组织相比,膀胱癌组织中miR-613的表达也下调。在35例膀胱癌组织中,与相邻组织相比,27例miR-613表达下调。miR-613的异位表达抑制膀胱癌细胞的增殖和侵袭。此外,miR-613过表达增强上皮生物标志物E-钙黏蛋白的表达,并抑制间充质生物标志物波形蛋白、Snail和N-钙黏蛋白的表达。此外,我们确定鞘氨醇激酶1(SphK1)是膀胱癌细胞中miR-613的直接靶基因。恢复Sphk1可部分挽救miR-613抑制的膀胱癌细胞增殖、侵袭和上皮-间质转化。
这些数据表明,miR-613通过靶向膀胱中的SphK1在膀胱癌中发挥肿瘤抑制作用。