Jiang Zhangjie, Zhang Yida, Cao Runfu, Li Li, Zhong Kezhao, Chen Qingsheng, Xiao Jianjun
Oncol Res. 2017 Aug 7;25(7):1081-1087. doi: 10.3727/096504016X14831120463349. Epub 2017 Jan 20.
miRNAs play a key role in the carcinogenesis of many cancers, including bladder cancer. In the current study, the role of miR-5195-3p, a quite recently discovered and poorly studied miRNA, in the proliferation and invasion of human bladder cancer cells was investigated. Our data displayed that, compared with healthy volunteers (control) and SU-HUC-1 normal human bladder epithelial cells, miR-5195-3p was sharply downregulated in bladder cancer patients and five human bladder cancer cell lines. The oligo miR-5195-3p mimic or miR-5195-3p antagomir was subsequently transfected into both T24 and BIU-87 bladder cancer cell lines. The miR-5195-3p mimic robustly increased the miR-5195-3p expression level and distinctly reduced the proliferation and invasion of T24 and BIU-87 cells. In contrast, the miR-5195-3p antagomir had an opposite effect on miR-5195-3p expression, cell proliferation, and invasion. Our data from bioinformatic and luciferase reporter gene assays identified that miR-5195-3p targeted the mRNA 3'-UTR of Krüppel-like factor 5 (KLF5), which is a proven proto-oncogene in bladder cancer. miR-5195-3p sharply reduced KLF5 expression and suppressed the expression or activation of its several downstream genes that are kinases improving cell survival or promoting cell cycle regulators, including ERK1/2, VEGFA, and cyclin D1. In conclusion, miR-5195-3p suppressed proliferation and invasion of human bladder cancer cells via suppression of KLF5.
微小RNA(miRNAs)在包括膀胱癌在内的多种癌症的致癌过程中发挥关键作用。在本研究中,我们调查了miR-5195-3p(一种最近才发现且研究较少的miRNA)在人膀胱癌细胞增殖和侵袭中的作用。我们的数据显示,与健康志愿者(对照)和SU-HUC-1正常人膀胱上皮细胞相比,miR-5195-3p在膀胱癌患者和5种人膀胱癌细胞系中显著下调。随后将寡聚miR-5195-3p模拟物或miR-5195-3p拮抗剂转染到T24和BIU-87膀胱癌细胞系中。miR-5195-3p模拟物显著提高了miR-5195-3p的表达水平,并明显降低了T24和BIU-87细胞的增殖和侵袭能力。相反,miR-5195-3p拮抗剂对miR-5195-3p表达、细胞增殖和侵袭具有相反的作用。我们通过生物信息学和荧光素酶报告基因分析的数据确定,miR-5195-3p靶向Krüppel样因子5(KLF5)的mRNA 3'-非翻译区,KLF5是膀胱癌中已证实的原癌基因。miR-5195-3p显著降低KLF5表达,并抑制其几个下游基因的表达或激活,这些下游基因是改善细胞存活或促进细胞周期调节的激酶,包括ERK1/2、VEGFA和细胞周期蛋白D1。总之,miR-5195-3p通过抑制KLF5抑制人膀胱癌细胞的增殖和侵袭。