EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway

Abstract

Background: The erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overexpressed in some malignant tumors and is associated with disease prognosis. However, the role of EphA5 in esophageal squamous cell carcinoma (ESCC) is not clear. Methods: In the present study, we measured the expression of EphA5 in ESCC tissues and cell lines including KYSE150 and KYSE450 cells. siRNA transfection was used to interfere with EphA5 expression in ESCC cell lines. Cell viability, colony formation, scratch and invasion assays were performed to explore the roles of EphA5 in ESCC cell lines. Flow cytometry analysis was performed to investigate whether EphA5 could affect the cell apoptosis and cycle. The biomarkers related to epithelial-mesenchymal transition (EMT) and molecules associated with Wnt/β-catenin signaling were also measured by western blot and immunofluorescence. Results: The protein and mRNA expression of EphA5 were significantly higher in fresh ESCC tissues and cell lines compared with normal control groups and human normal esophageal epithelial cells (HEEC). The cell viability assay and colony formation assay revealed that EphA5 knockdown enhanced the proliferation of KYSE150 and KYSE450 cells in vitro. The invasion and migration of ESCC cells were accelerated after EphA5 knockdown. The expression of EMT biomarkers was altered in ESCC cells transfected with siRNA targeting EphA5. Moreover, EphA5 downregulation enhanced the protein levels of β-catenin and p-GSK-3β Ser9 , which play a key role in the Wnt/β-catenin pathway. Conclusions: EphA5 knockdown promotes the proliferation of esophageal squamous cell carcinoma,enhances invasion and migration ability via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway.

Construction of Circular RNA–MicroRNA–Messenger RNA Regulatory Network of Recurrent Implantation Failure to Explore Its Potential Pathogenesis

“…The high expression of circRNA-000911 could antagonize miR-449a, thereby increasing Notch1 expression to inhibit cell proliferation, migration, and invasion and to promote apoptosis of breast cancer cells. Lu H. et al ( 2020 ) found that CIRS-126 regulated the expression of programmed cell death protein 4 (PDCD4) and inhibited the proliferation of ovarian granulosa cells by acting as a miR-21 sponge in polycystic ovary syndrome. In summary, circRNA–miRNA–messenger RNA (mRNA) regulatory network plays an important role in the occurrence and development of gynecologic diseases, while circRNA has different targets and functions in different tissue cells.…”

Expression of EPHA5 in lung adenocarcinoma is associated with lymph node metastasis and EGFR mutation

“…The cell viability and invasion and migration ability of esophageal cancer cells were accelerated after EPHA5 knockdown by siRNA. More recently, the roles of the EPHA5 receptor in lung cancer have been focused on [18,20,23,24]. EPHA5 expression was checked in lung cancer cell lines and human non-small cell lung cancer TMA (tissue microarray) specimens [18].…”

“…EPHA5 mRNA and protein expression were measured in esophageal squamous cell carcinoma cell lines and tissues. High expression of EPHA5 was found in esophageal squamous cell carcinoma tissues and cell lines [23]. The cell viability and invasion and migration ability of esophageal cancer cells were accelerated after EPHA5 knockdown by siRNA.…”

Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma

“…This leads to the activation of the Wnt/β-catenin signaling pathway, downstream LEF/TCF transcriptional activity and the start of EMT process 10 . Many studies have indicated that the WNT signaling pathway can impinge the development of Esophageal squamous cell carcinoma through the EMT pathway [26][27][28][29] . Studies have also shown that PRDM5 can bind to the promoter of TWIST1 to affect its transcriptional activity 10 .…”