LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer
LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer
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DOI：
10.1002/jcb.28783
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发表时间：
2019-09-01
影响因子：
4
通讯作者：
Xu, Zekuan
中科院分区：
文献类型：
--
作者：
Li, Qiang;Ge, Yugang;Xu, Zekuan
胃癌是世界上最常见的恶性肿瘤之一，在我国发病率和死亡率都很高。LEM domain containing 1（LEMD1）是一种重要的肿瘤-睾丸抗原，在多种肿瘤中过表达，并促进肿瘤的进展。然而，LEMD 1的生物学特性仍有待于在GC中探索。通过使用癌症基因组图谱数据集和我们的人类微阵列数据集分析LEMD1表达和GC进展之间的联系。采用Kaplan-Meier曲线分析LEMD1表达与预后的关系。采用实时荧光定量PCR和Western blot检测LEMD 1的表达，采用细胞增殖和集落形成实验及5-乙炔基-2 '-脱氧尿嘧啶核苷（5-ethynyl-2'-deoxyuridine，5-EDU）分析GC细胞的增殖能力。流式细胞仪检测细胞周期和凋亡情况。此外，在裸鼠皮下植入的肿瘤模型中，用于证明LEMD 1在体内促进肿瘤增殖的作用。在这项研究中，我们证明了与正常组织和GES-1相比，GC组织和细胞中LEMD 1的表达水平增加。体内外实验表明LEMD1通过调节细胞周期和凋亡促进胃癌细胞增殖。此外，我们发现LEMD 1通过激活磷脂酰肌醇3激酶（PI3 K）/蛋白激酶B（AKT）信号通路调节细胞增殖。总之，我们的研究结果表明，LEMD1有助于GC增殖通过调节细胞周期和凋亡通过激活PI3K/AKT信号通路。LEMD1可能作为GC治疗的潜在靶点。
Gastric cancer (GC) is one of the most common cancers worldwide and has especially high morbidity and mortality in China. LEM domain containing 1 (LEMD1), an important cancer-testis antigen, has been reported to be overexpressed in various cancers and promotes the progression of cancers. However, the biological characteristics of LEMD1 remain to be explored in GC. The connection between LEMD1 expression and GC progression was analyzed by using The Cancer Genome Atlas datasets and our human microarray datasets. A Kaplan-Meier plot was used to analyze the relationship between LEMD1 expression and prognosis. The expression of LEMD1 was analyzed by quantitative real-time polymerase chain reaction and Western blot, and the proliferation ability of GC cells was analyzed by cell proliferation and colony formation assays and 5-ethynyl-2 '-deoxyuridine analysis. The cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, subcutaneously implanted tumor models in nude mice were used to demonstrate the role of LEMD1 in promoting tumor proliferation in vivo. In this study, we demonstrated that the LEMD1 expression level was increased in GC tissues and cells compared with normal tissues and GES-1. The in vivo and in vitro assays showed that LEMD1 promoted GC cell proliferation by regulating the cell cycle and apoptosis. Moreover, we showed that LEMD1 regulated cell proliferation by activating the phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) signaling pathway. Overall, the results of our study suggest that LEMD1 contributes to GC proliferation by regulating the cell cycle and apoptosis via activation of the PI3K/AKT signaling pathway. LEMD1 may act as a potential target for GC treatment.