MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma

Abstract

Background: 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. Methods: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.Results: 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 apoptosisrelated 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. Conclusions:We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.

SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

“…A number of these, such as TUBB3 , encode targetable molecules that are being used in novel pharmacogenetic approaches in combination with other factors ( Karki et al, 2013 ). Others, such as MEX3A, may provide novel biomarkers or therapeutic targets ( Bufalieri et al, 2020 ; Wang et al, 2020 ; Yang et al, 2020 ). MEX3A controls the polarity and stemness and affects the cell cycle of intestinal epithelial cells through the downregulation of the mRNA encoding the CDX2 transcription factor ( Pereira et al, 2013 ) and, in addition, exhibits a transforming activity when overexpressed in gastric epithelial cells ( Jiang et al, 2012 ).…”

The Stemness Gene Mex3A Is a Key Regulator of Neuroblast Proliferation During Neurogenesis

“…In mice, mex3A is expressed in the crypt base and labels a slowly cycling subpopulation of Lgr5+ intestinal stem cell population (Barriga et al, 2017;Chatterji and Rustgi, 2018). MEX3A is overexpressed in pancreatic ductal adenocarcinoma (Wang et al, 2020) and strongly up-regulated in glioblastoma samples (Bufalieri et al, 2020). Despite this evidence, to our knowledge, there are no data available regarding the putative role of mex3a during embryonic and adult neurogenesis.…”

Oncogenic Potential of the Dual-Function Protein MEX3A

“…This could be facilitated by an altered PTEN function due to K27-linked ubiquitination mediated by MEX3A, as proposed for MEX3C [ 26 ], but further mechanistic studies are necessary to exclude a transcriptional or post-transcriptional regulation of EMT processes. Along this line, several reports indicate a role of MEX3A in the activation of the PIK3CA/AKT signaling pathway [ 67 , 74 , 75 , 82 ] that is involved in the regulation of, e.g., proliferation, metabolism, transcriptional control or cell migration (for review see [ 83 ]). Accordingly, MEX3A induced migratory phenotypes, as well as pronounced mesenchymal expression patterns, could be mediated by the activation of the AKT pathway affecting inter alia SNAI1, SNAI2 and TWIST levels [ 84 ], which are the main transcriptional drivers of EMT.…”