Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Acta Biochim Biophys Sin (Shanghai). 2019 May 23;51(5):492-500. doi: 10.1093/abbs/gmz030.
Ubiquitin E3 ligase membrane-associated RING-CH-type finger 7 (MARCH7), also known as axotrophin, was originally identified in mouse embryonic stem cells. MARCH7 is involved in T-cell proliferation, neuronal development, and the immune system. However, its role in endometrial cancer (EC) remains unclear. This study aimed to investigate the role of MARCH7 in EC. Quantitative polymerase chain reaction, immunohistochemistry, and western blot analysis were used to examine the expression of MARCH7, E-cadherin, Snail, and Vimentin in EC cell lines or clinical specimens. The role of MARCH7 in maintaining EC cell malignant phenotype was determined by transwell assay and using xenograft tumor model. Dual-luciferase reporter gene assay was performed to determine whether MARCH7 is an authentic target of miR-27b-3p. Our data showed that the expression level of MARCH7 in EC tissues was higher than that in normal endometrium tissues. The level of MARCH7 was positively associated with that of Snail and Vimentin, clinical stage, and histological grade, while negatively associated with that of E-cadherin. Knockdown of MARCH7 inhibited the invasion and metastasis of EC cells in vitro and in vivo. The opposite effect was observed after overexpressing MARCH7. MARCH7 promoted invasion and metastasis of EC cells via the Snail-mediated pathway. Furthermore, MARCH7 was demonstrated to be an authentic target of miR-27b-3p, and miR-27b-3p decreased the stimulus effect induced by MARCH7. These data indicate that MARCH7 may be an oncogenic factor and a therapeutic target for EC. miR-27b-3p/MARCH7 may also regulate EC cell invasion and metastasis via the Snail-mediated pathway.
泛素 E3 连接酶膜相关环指蛋白 7（MARCH7），也称为轴突营养因子，最初在小鼠胚胎干细胞中被发现。MARCH7 参与 T 细胞增殖、神经元发育和免疫系统。然而，其在子宫内膜癌（EC）中的作用尚不清楚。本研究旨在探讨 MARCH7 在 EC 中的作用。采用定量聚合酶链反应、免疫组织化学和 Western blot 分析检测 EC 细胞系或临床标本中 MARCH7、E-钙黏蛋白、Snail 和波形蛋白的表达。通过 Transwell 测定和异种移植肿瘤模型确定 MARCH7 在维持 EC 细胞恶性表型中的作用。双荧光素酶报告基因检测确定 MARCH7 是否为 miR-27b-3p 的真实靶标。我们的数据显示，EC 组织中 MARCH7 的表达水平高于正常子宫内膜组织。MARCH7 的水平与 Snail 和 Vimentin 的水平、临床分期和组织学分级呈正相关，而与 E-钙黏蛋白的水平呈负相关。敲低 MARCH7 抑制了 EC 细胞在体外和体内的侵袭和转移。过表达 MARCH7 则观察到相反的效果。MARCH7 通过 Snail 介导的途径促进 EC 细胞的侵袭和转移。此外，MARCH7 被证明是 miR-27b-3p 的真实靶标，miR-27b-3p 降低了 MARCH7 诱导的刺激作用。这些数据表明，MARCH7 可能是 EC 的致癌因子和治疗靶点。miR-27b-3p/MARCH7 也可能通过 Snail 介导的途径调节 EC 细胞的侵袭和转移。
