Published online Oct 7, 2018. doi: 10.3748/wjg.v24.i37.4263
Peer-review started: May 30, 2018
First decision: July 18, 2018
Revised: August 9, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 7, 2018
As one of the homeobox genes that play critical roles in the pattern formation of embryos, pancreatic-duodenal homeobox-1 (PDX1) is widely expressed in Brunner’s glands of the duodenum, pancreatic β cells, and gastric pyloric gland cells. PDX1 plays a key role in the development of the digestive system, including antrum, duodenum, and pancreas. Downregulation of PDX1 has been observed in gastric cancer, which suggests its potential role in gastric tumorigenesis. Nevertheless, the downstream mechanisms that mediate the effect of PDX1 on gastric tumorigenesis are still poorly understood.
Although PDX1 has been found to be involved in gastric tumorigenesis, its downstream regulating mechanism is still unclear.
To clarify the differential protein profile in PDX1-overexpressed gastric cell line and explore functional proteins involved in PDX1-mediated effects on gastric tumorigenesis.
A PDX1-overexpressed model was established using gastric cancer cell line SGC7901 (SGC-PDX1). As a method that is still widely used to identify cancer-associated proteins, 2DE-based proteomics was applied to determine the differential protein profile between SGC-PDX1 and SGC-pcDNA. The differential proteins were then subjected to qRT-PCR and immunoblotting for further confirmation. Finally, direct interactions between PDX1 and the identified differential proteins were evaluated by co-immunoprecipitation.
Seven proteins were found to be differentially expressed in SGC-PDX1 using 2-DE proteomics. Immunoblotting confirmed that the three differential HSPs (HSP70, HSP60, HSP27) were downregulated in SGC-PDX1. However, qRT-PCR analysis identified increased HSP mRNA in SGC-PDX1, which indicates that PDX1 may post-translationally regulate the expression of the HSPs. Further study is warranted to elucidate the relationship of HPS70 and PDX1, as co-immunoprecipitation did not identify direct interaction between them.
HSPs are involved in PDX1-mediated effects on the genesis of gastric cancer and the interaction between HSP70 and PDX1 is indirect.
This study demonstrates the involvement of HSPs in PDX1-mediated effects on gastric tumorigenesis. Further study is warranted to elucidate the downstream regulating mechanism of PDX1 on HSPs.