Overexpression of the cell growth regulator 1 with EF-hand domains inhibits the malignant behavior of colorectal cancer cells by suppressing the mitogen-activated protein kinase pathway
10.3760/cma.j.cn115396-20250124-00018
- VernacularTitle:过表达具有EF手域的细胞生长调节因子1通过丝裂原活化蛋白激酶抑制结直肠癌细胞的恶性行为
- Author:
Changhui JI
1
;
Yayan FU
;
Jun REN
;
Qiannan SUN
;
Chenyu LU
;
Daorong WANG
Author Information
1. 扬州大学附属苏北人民医院普通外科，扬州 225001
- Keywords:
Colonic neoplasms;
Cell proliferation;
Cell migration assays;
Immunity;
Mitogen-activated protein kinase kinases
- From:
International Journal of Surgery
2025;52(5):332-338
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects and potential mechanisms of cell growth regulator 1 ( CGREF1) with an EF hand domain in colorectal cancer proliferation and migration. Methods:Fifty paraffin specimens of colorectal cancer tissues and corresponding paracancerous tissues were selected from January 2023 to January 2024 from the Northern Jiangsu People's Hospital Affiliated to Yangzhou University for analysis, and TCGA, GDSC, KMPLOT and STRING databases were used to explore the expression, prognosis, immune microenvironment, drug sensitivity and related signaling pathway functions of CGREF1 in colorectal cancer. Tissue and cellular expression levels of CGREF1 were analyzed by immunohistochemistry and qRT-PCR. Lentiviral-mediated CGREF1 overexpression in SW-620 cells (OE- CGREF1 vs NC groups) was functionally characterized through CCK-8 proliferation assays, colony formation tests, and scratch wound healing migration assays, with mechanistic investigation via Western blot analysis of apoptosis markers, invasion-related proteins, and RAS/RAF/ERK pathway components. In vivo tumorigenicity was assessed by subcutaneous injection of control or CGREF1-overexpressing SW620 cells in nude mice ( n=3 per group) with tumor growth monitoring. Software of GraphPad Prism 9 was used for statistical analysis of experimental data. Results:CGREF1CGREF1RASERK Studies based on databases, clinical samples and colorectal cancer cell line analyses demonstrated that CGREF1 is downregulated in colorectal cancer, where low CGREF1 expression showed positive correlation with tumor diameter and invasion depth. CGREF1 is closely related to tumor immune infiltration microenvironment and sensitivity to multiple anti-tumor drugs. Overexpression of CGREF1 promoted cell apoptosis while inhibiting cell proliferation, invasion and migration. Overexpression of CGREF1 downregulated the expression levels of RAS, ERK and P-P38/MAPK pathway proteins. CGREF1 inhibited tumor growth in vivo. Conclusion:CGREF1 can inhibit the proliferation, colony formation, and migration of CRC cells through the RAS/ERK/MAPK pathway.
