MiR-27b-3p/MARCH7 regulates invasion and metastasis of endometrial cancer cells through Snail-mediated pathway.

Abstract

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.