FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway.
10.12122/j.issn.1673-4254.2023.06.13
- Author:
Hao ZHANG
1
;
Zhen ZHANG
1
;
Qiusheng WANG
1
;
Lian WANG
1
;
Zi YANG
1
;
Zhijun GENG
2
;
Yueyue WANG
3
;
Jing LI
3
;
Lugen ZUO
1
Author Information
1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
2. Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
3. Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
- Publication Type:Journal Article
- Keywords:
Gastric cancer;
four-jointed box kinase 1;
proliferation;
survival prognosis
- MeSH:
Animals;
Mice;
Cell Proliferation;
Ki-67 Antigen;
Mice, Nude;
Phosphatidylinositol 3-Kinases;
Proto-Oncogene Proteins c-akt;
Signal Transduction;
Stomach Neoplasms/pathology*;
Humans;
Intercellular Signaling Peptides and Proteins/genetics*
- From:
Journal of Southern Medical University
2023;43(6):975-984
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.
METHODS:The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.
RESULTS:GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).
CONCLUSION:FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.
