Zhang Yao, Zhang Wen, Xu Aiming, Tian Ye, Liang Chao, Wang Zengjun
Department of Urology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
School of Basic Medical Sciences, Nanjing Medical University Nanjing 211166, China.
Am J Transl Res. 2019 Aug 15;11(8):5019-5028. eCollection 2019.
Recent evidences suggested that miRNAs process key roles in the biological behaviors and the development of prostate carcinoma (PC). However, its molecular mechanism in PC is still remained largely unclear. In this study, the expression level of miR-188 and the protein expression of MARCKS were detected by RT-PCR and western blot, respectively. Moreover, we determined the oncogene or anti-oncogene role of miR-188 in the PC through gain and loss function assay of miR-188 using transfection of miR-188 mimics and inhibitor. Meanwhile, luciferase reporter vectors with miR-188 mimics were constructed and transfected into PC cells. Our data indicated that the expression of miR-188 was dramatically reduced in human PC tissues and cell lines and the increased miR-188 levels obviously inhibited the proliferation, migration and invasion of PC cells and negatively regulative with MARCKS. Together, our findings proved that miR-188 plays an inhibitive role in PC of proliferation, migration and invasion at least in part via suppressing MARCKS expression, which could be regarded as a promising therapeutic target in PC.
近期证据表明，微小RNA（miRNAs）在前列腺癌（PC）的生物学行为和发展过程中发挥关键作用。然而，其在前列腺癌中的分子机制仍 largely不清楚。在本研究中，分别通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测了miR-188的表达水平和丙酰肌醇磷脂结合蛋白激酶Cα（MARCKS）的蛋白表达。此外，我们通过转染miR-188模拟物和抑制剂对miR-188进行功能获得和缺失实验，确定了miR-188在前列腺癌中的致癌或抑癌作用。同时，构建了携带miR-188模拟物的荧光素酶报告载体并转染至前列腺癌细胞中。我们的数据表明，miR-188在人前列腺癌组织和细胞系中的表达显著降低，miR-188水平的升高明显抑制了前列腺癌细胞的增殖、迁移和侵袭，并与MARCKS呈负调控关系。总之，我们的研究结果证明，miR-188至少部分通过抑制MARCKS表达在前列腺癌的增殖、迁移和侵袭中发挥抑制作用，这可被视为前列腺癌一个有前景的治疗靶点。
