MARCH1 Interacts with β-Catenin as a New Oncogene for Gastric Cancer

Abstract

Background:Membrane-associated RING-CH 1 (MARCH1) is an E3 ubiquitin ligase that plays an important role in antigen presentation. The latest research found that MARCH1 can either promote or suppress cancer progression in ovarian, liver, and bladder cancers, but its function in gastric cancer has not been addressed. This study aimed to investigate the role of MARCH1 in gastric cancer.Methods:The Cancer Genome Atlas (TCGA) database was used to evaluate the expression level and biological function of MARCH1 in gastric cancer. We down-regulated and up-regulated the expression level of MARCH1 in gastric cancer cell line AGS by transfecting siRNAs and overexpression plasmids. Then we detected cell proliferation, migration, invasion and apoptosis using CCK-8 assay, transwell chamber assay and flow cytometry respectively. The relationship between MARCH1 and β-catenin was analyzed using western blotting assay. Results:The results showed that the expression of MARCH1 in gastric cancer was elevated and significantly related to clinical stage, tumor grade, and lymph node metastasis. It is worth noting that there was no significant correlation between the increase in MARCH1 expression level and overall survival. In addition, knocking down and upregulating the expression level of MARCH1 significantly affected the proliferation, migration, invasion, and apoptosis of gastric cancer cells. Furthermore, the study found that MARCH1 and β-catenin positively regulated each other, suggesting that MARCH1 may participate in the malignant biological behavior of tumors through the Wnt/β-catenin pathway.Conclusions:In summary, this study shows the function of MARCH1 in the progression of gastric cancer and provides unique insights into the regulatory mechanism of MARCH1 and β-catenin, which indicates that MARCH1 may be a new target molecule for gastric cancer.