Jin Lu, Zhou Yibin, Chen Guangqiang, Dai Guangcheng, Fu Kai, Yang Dongrong, Zhu Jin
Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, China.
Front Oncol. 2021 Feb 22;10:592239. doi: 10.3389/fonc.2020.592239. eCollection 2020.
Trophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We analyzed expressions of TROAP and other genes in prostate cancer tumors at different stages and assessed Gleason scores. We used Celigo image, Transwell, and rescue assays, and flow cytometry detection to assess growth, apoptosis, proliferation, migration, and invasion of the prostate cancer cells. We identified and validated up- and down-stream genes in the TROAP pathway. The mRNA data suggested that TROAP expression was markedly upregulated in prostate cancer compared with its expression in normal tissues, especially in cancers with high stages and Gleason scores. Moreover, a high TROAP expression was associated with poor patient survival. Results of our assay showed that TROAP knockdown inhibited DU145 and PC3 cell proliferation and viability cell apoptosis and S phase cycle arrest. The Transwell assay showed that TROAP knockdown inhibited cell migration and invasion, probably through MMP-9 and E-Cadherin modulation. Overexpression of TWIST partially abrogated the inhibitory effects of TROAP knockdown on prostate cancer cells. Our integrative mechanism dissection revealed that TROAP is in a pathway downstream of EZH2 and that it activates the TWIST/c-Myc pathway to regulate prostate cancer progression. In all, we identified TROAP as a driver of prostate cancer development and progression, providing a novel target for prostate cancer treatments.
肌动蛋白相关蛋白（TROAP）已被证明在某些肿瘤中过表达并促进肿瘤进展。我们进行了这项研究以评估TROAP在前列腺癌中的生物学和临床意义。我们从TCGA和GEO数据库下载了TROAP mRNA表达数据。我们分析了不同阶段前列腺癌肿瘤中TROAP和其他基因的表达，并评估了 Gleason评分。我们使用Celigo图像、Transwell和挽救试验以及流式细胞术检测来评估前列腺癌细胞的生长、凋亡、增殖、迁移和侵袭。我们鉴定并验证了TROAP途径中的上游和下游基因。mRNA数据表明，与正常组织相比，前列腺癌中TROAP的表达明显上调，尤其是在高分期和高Gleason评分的癌症中。此外，TROAP高表达与患者生存率低相关。我们的试验结果表明，TROAP敲低抑制了DU145和PC3细胞的增殖和活力、细胞凋亡以及S期细胞周期阻滞。Transwell试验表明，TROAP敲低抑制了细胞迁移和侵袭，可能是通过调节MMP-9和E-钙黏蛋白。TWIST的过表达部分消除了TROAP敲低对前列腺癌细胞的抑制作用。我们的综合机制剖析表明，TROAP位于EZH2的下游途径中，并且它激活TWIST/c-Myc途径来调节前列腺癌的进展。总之，我们确定TROAP是前列腺癌发展和进展的驱动因素，为前列腺癌治疗提供了一个新的靶点。
