Wang Xueling, Shi Zhimin, Liu Xiaoxia, Su Ying, Li Weixia, Dong Haiping, Zhao Liwei, Li Manman, Wang Yunxiao, Jin Xiu, Huo Zhongchao
Department of Laboratory Medicine, Medical Technology Affiliated Hospital, College of Medicine, Hebei University of Engineering, Handan 056002, P.R.China.
J BUON. 2018 Mar-Apr;23(2):444-452.
Prostate cancer (PCa) is the most frequently malignant neoplasm in men. MicroRNAs (miRs) have been identified to play important biological roles in a variety of tumors. Several studies showed that miR-191 was involved in the development of different cancers, but its role in prostate cancer remains unclear.
Human PCa cell lines DU145, PC-3 and LNCAP, and benign prostate hyperplasia (BPH) and human prostate epithelial cell line RWPE-1 were used. The expression level of miR-191 in 48 paired prostate tumor and adjacent normal tissues was assessed along with the clinical patient features. Synthetic miR-191 mimics and inhibitors were used to overexpress or inhibit the miR-191 level. CCK8 and colony formation assay were used to evaluate the cell growth. The ability of cell invasion was studied by transwell assay. Dual-luciferase experiment was used to identify the target gene and western blot was performed to evaluate the protein level.
miR-191 was overexpressed in PCa tissue samples compared to the normal group as well in PCa-derived cell lines. Upregulation miR-191 in PC-3 cells significantly promoted while downregulation miR-191 in DU145 cells retarded the cell proliferation and invasion. Furthermore, TIMP3 were proved to be a direct target gene of miR-191 and knockdown of TIMP3 reversed the function of miR-191 downregulation.
This study demonstrated that miR-191 promoted the cell growth and invasion ability in prostate cancer through downregulating TIMP3 and might be a potential target for the biotherapy for PCa.
前列腺癌（PCa）是男性中最常见的恶性肿瘤。微小RNA（miRs）已被证实可在多种肿瘤中发挥重要的生物学作用。多项研究表明，miR-191参与了不同癌症的发展，但其在前列腺癌中的作用仍不明确。
使用人前列腺癌细胞系DU145、PC-3和LNCAP，以及良性前列腺增生（BPH）和人前列腺上皮细胞系RWPE-1。评估48对前列腺肿瘤组织和相邻正常组织中miR-191的表达水平，并分析临床患者特征。使用合成的miR-191模拟物和抑制剂来上调或抑制miR-191水平。采用CCK8和集落形成试验评估细胞生长情况。通过Transwell试验研究细胞侵袭能力。采用双荧光素酶实验鉴定靶基因，并进行蛋白质免疫印迹法评估蛋白质水平。
与正常组相比，miR-191在前列腺癌组织样本以及前列腺癌衍生的细胞系中均过表达。PC-3细胞中miR-191的上调显著促进了细胞增殖和侵袭，而DU145细胞中miR-191的下调则抑制了细胞增殖和侵袭。此外，TIMP3被证明是miR-191的直接靶基因，敲低TIMP3可逆转miR-191下调的功能。
本研究表明，miR-191通过下调TIMP3促进前列腺癌细胞的生长和侵袭能力，可能是前列腺癌生物治疗的潜在靶点。
