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Published on: March 15, 2024
CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
Yingying Zhao1, Rui Ma1, Chuyue Wang1
1Guangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Purpose:
Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CRC.
Methods:
Bioinformatic analysis of gene expression was conducted using the UALCAN website. Cell proliferation was measured using the CCK-8 kit. Cell cycle, apoptosis, and ferroptosis were analyzed using flow cytometry. Tumorigenesis was evaluated by the subcutaneous inoculation of CRC cells into BALB/c nude female mice. Differentially expressed genes and signaling pathways were identified using RNA sequencing.
Results:
CAPG was significantly overexpressed in human CRC tissues and its upregulation was correlated with poor overall survival. CAPG knockdown led to notable inhibition of CRC cells in vitro and in vivo. Interference with CAPG blocked the cell cycle at the G1 phase and triggered apoptosis and ferroptosis by upregulating the P53 pathway in CRC cells.
Conclusion:
CRC patients with higher CAPG levels have a poorer prognosis. CAPG inhibits apoptosis and ferroptosis, while promoting CRC cell proliferation by repressing the P53 pathway. Our study suggests that CAPG may be a potential therapeutic target for CRC prognosis and treatment.
Insights
Capping Actin Protein (CAPG) is overexpressed in colorectal cancer (CRC), promoting tumor growth. Inhibiting CAPG halts CRC cell proliferation and triggers cell death, suggesting CAPG as a promising therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Colorectal cancer (CRC) presents high incidence and mortality rates.
- Existing treatments for CRC are inadequate for many patients.
- Capping Actin Protein (CAPG) plays a role in actin dynamics.
Purpose of the Study:
- Investigate Capping Actin Protein (CAPG) as a novel therapeutic target for colorectal cancer (CRC).
- Determine the role of CAPG in CRC progression and patient prognosis.
Main Methods:
- Utilized bioinformatic analysis (UALCAN) for gene expression profiling.
- Assessed cell proliferation, cell cycle, apoptosis, and ferroptosis via CCK-8 assay and flow cytometry.
- Evaluated tumorigenesis in vivo using mouse models and identified differentially expressed genes/pathways through RNA sequencing.
Main Results:
- CAPG was significantly overexpressed in CRC tissues, correlating with poor overall survival.
- CAPG knockdown inhibited CRC cell proliferation both in vitro and in vivo.
- CAPG interference blocked the cell cycle at G1 phase and induced apoptosis and ferroptosis via the P53 pathway.
Conclusions:
- Elevated CAPG levels in CRC patients indicate a poorer prognosis.
- CAPG promotes CRC proliferation by suppressing the P53 pathway, while inhibiting apoptosis and ferroptosis.
- CAPG represents a potential therapeutic target for improving CRC prognosis and treatment outcomes.
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