4.7 Article

MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma

Journal

CANCER CELL INTERNATIONAL
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12935-020-1146-x

Keywords

PDA; MEX3A; Proliferation; Colony formation; Apoptosis; Migration

Categories

Funding

  1. Key Research and Development Projects in Sichuan Province [2019YFS0043]
  2. Key Research Program Foundation of Science and Technology Commission of Sichuan Province [2017SZ0107]
  3. Zhejiang Province Public Welfare Technology Research Project [2016C33208]
  4. Post-Doctor Research Project, West China Hospital, Sichuan University [2019HXBH044]
  5. China Postdoctoral Science Foundation [2019M663519]
  6. 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZY2017302-1.3.5]

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

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