Open AccessGolgi scaffold protein PAQR3 as a candidate suppressor of gastric cardia adenocarcinoma via regulating TGF ‐β/Smad pathway
Author(s) -
Wu YingLi,
Hong LianLian,
Ling ZheNan,
Hu XuanYu,
Liu Zhu,
Li Pei,
Ling ZhiQiang
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24617
Subject(s) - smad , chemistry , western blot , microbiology and biotechnology , downregulation and upregulation , biology , signal transduction , biochemistry , gene
Objectives To investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial–mesenchymal transition (EMT). Methods We detected PAQR3 protein in 146 GCA tissues and paired normal adjacent tissues (PNTs) specimens using immunohistochemical analysis, and explored its clinical significance. The expression levels of PAQR3 protein in 20 GCA tissues, their paired PNTs, HGC27, SGC7901, and GES‐1 cells were analyzed by Western blot. Wild‐type PAQR3 was overexpressed in HGC27 cells. The effects of PAQR3 overexpression on the function of HGC27 cells and its underlying mechanisms were then analyzed through a series of cell and molecular biology experiments. Results PAQR3 was significantly down‐regulated in GCA tissues when compared with paired PNTs ( p < 0.0001). The expression level of PAQR3 in GCA tissues was significantly negatively correlated with Helicobacter pylori infection ( p = 0.000), venous invasion ( p = 0.000), invasion depth ( p = 0.000), lymph node metastasis ( p = 0.022), tumor stage ( p = 0.000), and patient survival ( p = 0.009). Downregulation of PAQR3 was highly correlated with increased EMT signature and activated TGF‐β/Smad pathway in GCA tissues. Overexpression of PAQR3 in HGC27 cells negatively regulates its cellular functions, such as cell proliferation and migration, and suppresses EMT. Mechanistically, overexpression of PAQR3 significantly down‐regulates the protein expression levels of TGF‐1, p‐Smad2, and p‐Smad3 in HGC27 cells. Conclusion PAQR3 was significantly down‐regulated in GCA tissues, HGC27, and SGC7901 cells. PAQR3 significantly inhibits the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 can inhibit the EMT process in HGC27 cells by regulating TGF‐β/Smad signaling pathway.