SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2

Abstract

Colorectal cancer (CRC), a common malignant tumor in the digestive tract, is a leading cause of cancer-related death. <i>SPRY4</i> has been reported to act as a tumor suppressor gene in various tumors. This study aims to assess the role of SPRY4 in colorectal cancer (CRC) and uncover its underlying mechanisms. Firstly, the expression levels of <i>SPRY4</i> were measured in CRC cell lines. <i>SPRY4</i>-overexpressing or silencing plasmids were transfected into CRC cells to regulate its expression level. CCK-8, colony formation, EdU assay, wound-healing and Transwell assays were performed to determine cell proliferation, invasion and migration abilities. Then, apoptosis was measured by flow cytometry analysis, and the expression of apoptosis-related protein was analyzed by western-blotting. Next, the <i>in vivo</i> tumorigenesis assay was performed in nude mice. According to the results, there was a lower expression of <i>SPRY4</i> in CRC cell lines compared with normal cell line, and the overexpression of <i>SPRY4</i> significantly suppressed cell proliferation, migration and invasion, and promoted apoptosis in SW480 cells. Moreover, the enhanced proliferation, invasion and migration upon <i>SPRY4</i> silencing was reversed by <i>EZH2</i> inhibition. In addition, we found that the overexpression of <i>SPRY4</i> inhibited tumorigenesis <i>in vivo</i> by diminishing the size and weight of the tumors. Our study indicates that <i>SPRY4</i> might be a potential tumor suppressor gene and prognostic factor for patients with CRC.