Zeng Rong, Liu Yi, Jiang Zhao-Jing, Huang Jun-Peng, Wang Yu, Li Xu-Feng, Xiong Wei-Bin, Wu Xiao-Cong, Zhang Ji-Ren, Wang Qi-En, Zheng Yan-Fang
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510280, P.R. China.
Int J Oncol. 2018 May;52(5):1443-1454. doi: 10.3892/ijo.2018.4316. Epub 2018 Mar 14.
Although there have been reports about the role of erythrocyte membrane protein band 4.1 like 3 (EPB41L3) in several types of cancer, primarily in non-small-cell lung carcinoma, the molecular function and modulatory mechanisms of EPB41L3 remain unclear. In specific, the functional and clinical significance of EPB41L3 in esophageal squamous cell carcinoma (ESCC) has not been explored to date. In the present study, reduced EPB41L3 expression was demonstrated in ESCC cell lines and tissues, which was due to its high methylation rate. Ectopic expression of EPB41L3 in ESCC cells inhibited cell proliferation in vivo and in vitro. In addition, EPB41L3 overexpression induced apoptosis and G2/M cell cycle arrest by activating Caspase-3/8/9 and Cyclin-dependent kinase 1/Cyclin B1 signaling, respectively. Notably, patients with higher EPB41L3 expression had markedly higher overall survival rates compared with patients with lower EPB41L3 expression. In summary, the present results suggest that EPB41L3 may be a tumor suppressor gene in ESCC development, representing a potential therapeutic target and a prognostic indicator for ESCC.
尽管已有报道称红细胞膜蛋白带4.1样蛋白3（EPB41L3）在几种类型的癌症中发挥作用，主要是在非小细胞肺癌中，但EPB41L3的分子功能和调节机制仍不清楚。具体而言，EPB41L3在食管鳞状细胞癌（ESCC）中的功能和临床意义迄今尚未得到探索。在本研究中，ESCC细胞系和组织中显示出EPB41L3表达降低，这是由于其高甲基化率所致。EPB41L3在ESCC细胞中的异位表达在体内和体外均抑制细胞增殖。此外，EPB41L3过表达分别通过激活半胱天冬酶-3/8/9和细胞周期蛋白依赖性激酶1/细胞周期蛋白B1信号传导诱导细胞凋亡和G2/M期细胞周期阻滞。值得注意的是，与EPB41L3表达较低的患者相比，EPB41L3表达较高的患者总体生存率明显更高。总之，目前的结果表明，EPB41L3可能是ESCC发生发展中的一种肿瘤抑制基因，是ESCC潜在的治疗靶点和预后指标。
