Endothelial cell-specific molecule 1 promotes the epithelial-mesenchymal transition of cervical cancer via ZEB1

Aim: This study aimed to investigate the mechanism of endothelial cell-specific molecule 1 (ESM1) promoting cervical cancer cell proliferation and epithelial-mesenchymal transition (EMT) characteristics through zinc finger E-box binding homeobox 1 (ZEB1)/EMT pathway. Objective The anticancer mechanism of aloe-emodin (AE) and its relationship with ESM1/ZEB1 signaling pathway were analyzed. Method In this study, the correlation between ESM1 expression and the prognosis of cervical cancer patients were analyzed by bioinformatics. Herein, SiHa, HeLa cell lines, and corresponding control cell lines with stable ESM1 expression were obtained. The CCK-8 assay was used to detect cell proliferation ability. In addition, the invasion and migration ability of Hela and SiHa cells were detected by Transwell assay and scratch closure assay. Meanwhile, real-time PCR was used to detect expressions of EMT-related markers E-cadherin and Vimentin. The ability of silenced ESM1 to tumor formation in vivo was detected by tumor formation in nude mice. The same method was used to analyze the effects of aloe-emodin (AE) on inhibiting ESM1 expression and its inhibitory effect on cervical cancer cells in vitro and in vivo. ESM1 was highly expressed in cervical cancer, and the high expression of ESM1 was associated with poor prognosis in cervical cancer patients. Result CCK-8 results showed that the proliferation, invasion, and migration of Hela and SiHa cells were reduced after siRNA interfered with ESM1 expression. Overexpression of ESM1 promoted the proliferation and migration of cervical cancer cells. Mechanism studies have shown that the oncogenic effect of ESM1 was realized through the ZEB1/PI3K/AKT pathway. High throughput drug screening found that AE can target ESM1. Inhibitory effect of AE on ESM1/ZEB1/EMT signaling pathway and cervical cancer cells. Conclusion The silencing of ESM1 expression may inhibit the proliferation, invasion, metastasis, and epithelial-mesenchymal transformation of cervical cancer cells by inhibiting ZEB1/PI3K/AKT. AE is a potential treatment for cervical cancer, which can play an anti-tumor role by inhibiting ESM1/ZEB1 axis.