Suppression of BMX-ARHGAP fusion gene inhibits epithelial-mesenchymal transition in gastric cancer cells via RhoA-mediated blockade of JAK/STAT axis

Abstract

Gastric cancer (GC) is one of the main causes of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) is an important biological process involving the process by which malignant tumor cells obtain the ability of migration, invasion, resistance of apoptosis, and degradation in the extracellular matrix. The current study aimed at investigating whether bone marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene affects GC. First, short hairpin RNA (shRNA) against BMX-ARHGAP or BMX-ARHGAP were introduced to treat SGC-7901 cells with the highest BMX-ARHGAP among the five GC cell lines (SGC-7901, MKN-45, NCI-N87, SNU-5, and AGS). Next, cell vitality, drug resistance, migration, and invasion of SGC-7901 cells, activities of Rho and JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The survival rate of the mice was then determined through the transfection of the specific pathogen-free NOD-SCID mice with treated SGC-7901 cells. The results showed that BMX-ARHGAP expression was associated with the infiltration degree of GC tumor and poor prognosis for patients with GC. BMX-ARHGAP silencing was found to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality, drug resistance, migration and invasion, reverse EMT process, as well as inhibit LNM. BMX-ARHGAP overexpression was observed to have induced effects on GC cells as opposed to those inhibited by BMX-ARHGAP silencing. The survival rate of mice was increased after transfection with silenced BMX-ARHGAP. These findings provided evidence that the suppression of BMX-ARHGAP resulted in the inhibition of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.

Keywords: JAK/STAT axis; RhoA; bone marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene; epithelial-mesenchymal transition (EMT); gastric cancer (GC).