Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou, 510800, China; Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou, 510800, China.
Biomed Pharmacother. 2018 Jun;102:531-538. doi: 10.1016/j.biopha.2018.03.079. Epub 2018 Mar 26.
Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is up-regulated in multiple human tumors. However, the expression, function and clinical significance of SRPK2 in prostate cancer (PCa) has not yet been understood. We therefore aimed to determine the association of SRPK2 with tumor progression and metastasis in PCa patients in our present study. The expression of SRPK2 was detected by some public datasets and validated using a clinical tissue microarray (TMA) by immunohistochemistry. The association of SRPK2 expression with various clinicopathological characteristics of PCa patients was subsequently statistically analyzed based on the The Cancer Genome Atlas (TCGA) dataset and clinical TMA. The effects of SRPK2 on cancer cell proliferation, migration, invasion, cell cycle progression, apoptosis and tumor growth were then respectively investigated using in vitro and in vivo experiments. First, public datasets showed that SRPK2 expression was greater in PCa tissues when compared with non-cancerous tissues. Statistical analysis demonstrated that high expression of SRPK2 was significantly correlated with a higher Gleason Score, advanced pathological stage and the presence of tumor metastasis in the TCGA Dataset (all P < 0.01). Similar correlations between SRPK2 and a higher Gleason Score or advanced pathological stage were also identified in the TMA (P < 0.05). Kaplan-Meier curve analyses showed that the biochemical recurrence (BCR)-free time of PCa patients with SRPK2 high expression was shorter than for those with SRPK2 low expression (P < 0.05). Second, cell function experiments in PCa cell lines revealed that enhanced SRPK2 expression could promote cell proliferation, migration, invasion and cell cycle progression but suppress tumor cell apoptosis in vitro. Xenograft experiments showed that SRPK2 promoted tumor growth in vivo. In conclusion, our data demonstrated that SRPK2 may play an important role in the progression and metastasis of PCa, which suggests that it might be a potential therapeutic target for PCa clinical therapy.
丝氨酸/精氨酸丰富蛋白激酶-2（SRSF 蛋白激酶-2，SRPK2）在多种人类肿瘤中上调。然而，SRPK2 在前列腺癌（PCa）中的表达、功能和临床意义尚未得到理解。因此，在本研究中，我们旨在确定 SRPK2 与 PCa 患者肿瘤进展和转移的关系。通过一些公共数据集检测 SRPK2 的表达，并通过免疫组织化学法使用临床组织微阵列（TMA）进行验证。随后根据癌症基因组图谱（TCGA）数据集和临床 TMA 对 SRPK2 表达与 PCa 患者各种临床病理特征的关系进行统计学分析。然后分别通过体外和体内实验研究 SRPK2 对癌细胞增殖、迁移、侵袭、细胞周期进展、凋亡和肿瘤生长的影响。首先，公共数据集显示，与非癌组织相比，PCa 组织中 SRPK2 的表达更高。统计分析表明，在 TCGA 数据集（均 P<0.01）中，SRPK2 高表达与较高的 Gleason 评分、较晚期的病理分期和肿瘤转移的存在显著相关。在 TMA 中也发现了 SRPK2 与较高的 Gleason 评分或较晚期病理分期之间的相似相关性（P<0.05）。Kaplan-Meier 曲线分析显示，SRPK2 高表达的 PCa 患者的生化无复发生存时间短于 SRPK2 低表达的患者（P<0.05）。其次，在 PCa 细胞系中的细胞功能实验表明，增强的 SRPK2 表达可促进细胞增殖、迁移、侵袭和细胞周期进展，但抑制肿瘤细胞凋亡。异种移植实验表明，SRPK2 促进了体内肿瘤的生长。总之，我们的数据表明，SRPK2 可能在 PCa 的进展和转移中发挥重要作用，这表明它可能成为 PCa 临床治疗的潜在治疗靶点。
