Huang Wen, Wei Xiao-Long, Ni WeiWei, Cao Mengda, Meng Ling, Yang Haiwei
1 Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2 Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Tumour Biol. 2017 May;39(5):1010428317701635. doi: 10.1177/1010428317701635.
RBM38, a member of RNA recognition motif family of RNA-binding proteins, can regulate the expression of diverse targets by influencing their messenger RNA stability and play a vital role in cancer development. RBM38 may act as an oncogene or suppressor gene in several human tumors. However, its role in human renal cell carcinoma remains unclear. In this study, we found that the expression of RBM38 was lower in renal cell carcinoma tissues and cell lines. Moreover, overexpression of RBM38 could reduce, whereas knockdown of RBM38 could accelerate renal cell carcinoma cell lines growth rate and number of colonies formation of renal cell carcinoma cell lines. Furthermore, RBM38 inhibited renal cell carcinoma cell lines migration and invasion through epithelial-mesenchymal transition suppression by up-regulating E-cadherin and down-regulating β-catenin and vimentin. For in vivo assays, we found that the RBM38-positive group CAKI-1-RBM38 formed smaller tumors in nude mice compared with the control group. Kaplan-Meier analysis showed that renal cell carcinoma patients with lower expression of RBM38 had a significantly shorter survival time than those with higher expression of RBM38 ( p = 0.028). All these suggested that RBM38 acts as a tumor suppressor in renal cell carcinoma, which has the potential value for the prediction of renal cell carcinoma prognosis.
RBM38是RNA结合蛋白的RNA识别基序家族成员之一，可通过影响信使RNA稳定性来调节多种靶标的表达，并在癌症发展中发挥重要作用。RBM38在几种人类肿瘤中可能作为癌基因或抑癌基因。然而，其在人类肾细胞癌中的作用仍不清楚。在本研究中，我们发现RBM38在肾细胞癌组织和细胞系中的表达较低。此外，RBM38的过表达可降低肾细胞癌细胞系的生长速率和集落形成数量，而敲低RBM38则可加速其生长。此外，RBM38通过上调E-钙黏蛋白、下调β-连环蛋白和波形蛋白，抑制上皮-间质转化，从而抑制肾细胞癌细胞系的迁移和侵袭。在体内实验中，我们发现与对照组相比，RBM38阳性组CAKI-1-RBM38在裸鼠体内形成的肿瘤较小。Kaplan-Meier分析显示，RBM38表达较低的肾细胞癌患者的生存时间明显短于RBM38表达较高的患者（p = 0.028）。所有这些表明，RBM38在肾细胞癌中起肿瘤抑制作用，对肾细胞癌预后的预测具有潜在价值。
