Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Exp Cell Res. 2020 Jul 15;392(2):112029. doi: 10.1016/j.yexcr.2020.112029. Epub 2020 Apr 21.
Renal cell carcinoma (RCC) is one of the most common malignant tumors in the urinary system, whose molecular mechanism is still not clear. ALPK2 is a member of alpha protein kinase family, and its relationship with RCC is never reported. In this study, expression of ALPK2 in tumor tissues or cells of RCC was detected by qPCR, western blotting and immunohistochemical analysis. The effects of ALPK2 knockdown on cell proliferation, colony formation, cell migration and apoptosis were assessed by MTT, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of ALPK2 knockdown on tumor growth in vivo was evaluated by mice xenograft models. The results demonstrated that ALPK2 was upregulated in tumor tissues of RCC and its high expression was significantly associated with advanced stage and poor prognosis. Knockdown of ALPK2 could inhibited cell proliferation, colony formation and cell migration of RCC cells, while promoting cell apoptosis. The suppression of tumor growth in vivo by ALPK2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of RCC by ALPK2 may involve Akt, CDK6, Cyclin D1 and PIK3CA signaling. Therefore, our studies suggested that ALPK2 may act as a tumor promotor in the development and progression of RCC, and could be considered as a novel therapeutic target for RCC treatment.
肾细胞癌（RCC）是泌尿系统中最常见的恶性肿瘤之一，其分子机制尚不清楚。ALPK2 是α蛋白激酶家族的成员，其与 RCC 的关系从未有报道。在本研究中，通过 qPCR、western blot 和免疫组织化学分析检测了 ALPK2 在 RCC 肿瘤组织或细胞中的表达。通过 MTT、集落形成实验、划痕愈合实验、Transwell 实验和流式细胞术分别评估了 ALPK2 敲低对细胞增殖、集落形成、细胞迁移和细胞凋亡的影响。通过小鼠异种移植模型评估了 ALPK2 敲低对体内肿瘤生长的影响。结果表明，ALPK2 在 RCC 肿瘤组织中上调，其高表达与晚期和预后不良显著相关。ALPK2 敲低可抑制 RCC 细胞的增殖、集落形成和细胞迁移，同时促进细胞凋亡。利用小鼠异种移植模型也显示了 ALPK2 敲低对体内肿瘤生长的抑制作用。此外，ALPK2 对 RCC 的调节可能涉及 Akt、CDK6、Cyclin D1 和 PIK3CA 信号通路。因此，我们的研究表明，ALPK2 可能在 RCC 的发生和发展中起肿瘤促进剂的作用，并可考虑作为 RCC 治疗的新的治疗靶点。
