High expression of CRTAC1 promotes proliferation, migration and immune cell infiltration of gastric cancer by regulating the PI3K/AKT signaling pathway.
10.12122/j.issn.1673-4254.2024.12.19
- Author:
Fuxing ZHANG
1
;
Guoqing LIU
1
;
Rui DONG
1
;
Lei GAO
1
;
Weichen LU
1
;
Lianxia GAO
1
;
Zhongkuo ZHAO
2
;
Fei LU
2
;
Mulin LIU
1
Author Information
1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
2. Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China.
- Publication Type:Journal Article
- Keywords:
CRTAC1;
epithelial-mesenchymal transition;
gastric cancer;
immune infiltration
- MeSH:
Stomach Neoplasms/metabolism*;
Humans;
Cell Proliferation;
Proto-Oncogene Proteins c-akt/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Signal Transduction;
Cell Movement;
Cell Line, Tumor;
Prognosis;
Apoptosis;
Tumor Microenvironment;
Female;
Male;
Epithelial-Mesenchymal Transition/genetics*
- From:
Journal of Southern Medical University
2024;44(12):2421-2433
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC.
METHODS:Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism.
RESULTS:Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (P<0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (P<0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (P<0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells.
CONCLUSIONS:High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition via modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.
