Xu Bin, Lu Xiaoming, Zhao Yuming, Liu Chunhui, Huang Xiaoming, Chen Shuqiu, Zhu Weidong, Zhang Lihua, Chen Ming
Department of Urology, School of Medicine, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, Jiangsu 210009, P.R. China.
Oncol Lett. 2019 Feb;17(2):1889-1895. doi: 10.3892/ol.2018.9791. Epub 2018 Dec 4.
Clinical management of metastatic prostate cancer remains a challenge. Activation of apoptosis signaling pathways via signal transducer and activator of transcription 6 (STAT6) has been hypothesized to be a therapeutic strategy for patients with metastatic prostate cancer. The ONCOMINE prostate cancer database and two Gene Expression Omnibus datasets (Gene Series 40026 and 21032) were re-analyzed to determine the expression levels of STAT6 and microRNA (miR)-135a in prostate cancer. The current study investigated the induced overexpression of miR-135a in prostate cancer cell lines to detect its function in prostate cell apoptosis using Hoechst staining and fluorescence-activated cell sorting and examined the expression levels of STAT6 and its DNA binding ability using western blotting and an electrophoretic mobility shift assay. In analysis of the ONCOMINE database, STAT6 expression levels in prostate cancer tissue were higher compared with those in normal prostate gland tissue and were associated with the overall survival rate and biochemical relapse rate following radical prostatectomy. Additionally, there was an inverse correlation between miR-135a and STAT6 expression levels in prostate cancer cell lines. miR-135a was able to induce prostate cancer cell apoptosis via targeting STAT6 mRNA and subsequently repressing protein expression and phosphorylation, which also altered the transcriptional factor function of STAT6 through its DNA-binding capabilities. In conclusion, miR-135a may function as a tumor-suppressing miRNA in prostate cancer and its anti-oncogenic activity may involve the direct targeting and inhibition of STAT6.
转移性前列腺癌的临床管理仍然是一项挑战。通过信号转导和转录激活因子6（STAT6）激活凋亡信号通路被认为是转移性前列腺癌患者的一种治疗策略。对ONCOMINE前列腺癌数据库和两个基因表达综合数据集（基因系列40026和21032）进行重新分析，以确定前列腺癌中STAT6和微小RNA（miR）-135a的表达水平。本研究通过Hoechst染色和荧光激活细胞分选研究了miR-135a在前列腺癌细胞系中的诱导过表达，以检测其在前列腺细胞凋亡中的作用，并通过蛋白质印迹和电泳迁移率变动分析检测了STAT6的表达水平及其DNA结合能力。在ONCOMINE数据库分析中，前列腺癌组织中STAT6的表达水平高于正常前列腺组织，且与前列腺癌根治术后的总生存率和生化复发率相关。此外，前列腺癌细胞系中miR-135a与STAT6表达水平呈负相关。miR-135a能够通过靶向STAT6 mRNA诱导前列腺癌细胞凋亡，随后抑制蛋白表达和磷酸化，这也通过其DNA结合能力改变了STAT6的转录因子功能。总之，miR-135a可能在前列腺癌中作为一种肿瘤抑制性微小RNA发挥作用，其抗癌活性可能涉及对STAT6的直接靶向和抑制。
