MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma

摘要

Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA. In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell. This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9. We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.