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.

中文翻译：

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CAPG干扰通过P53途径诱导结直肠癌细胞凋亡和铁死亡

目的

鉴于结直肠癌 (CRC) 的高发病率和死亡率以及许多患者现有治疗方法的不足，本研究旨在探索帽肌动蛋白 (CAPG)（一种参与肌动蛋白相关运动的蛋白质）作为一种新型治疗方法的潜力。 CRC 的治疗靶点。

方法

使用 UALCAN 网站进行基因表达的生物信息分析。使用CCK-8试剂盒测量细胞增殖。使用流式细胞术分析细胞周期、细胞凋亡和铁死亡。通过将 CRC 细胞皮下接种到 BALB/c 雌性裸鼠中来评估肿瘤发生。使用RNA测序鉴定差异表达基因和信号通路。

结果

CAPG 在人类结直肠癌组织中显着过度表达，其上调与较差的总体生存率相关。CAPG 敲除导致体外和体内CRC 细胞的显着抑制。干扰 CAPG 会阻断细胞周期在 G1 期，并通过上调 CRC 细胞中的 P53 途径引发细胞凋亡和铁死亡。

结论

CAPG水平较高的CRC患者预后较差。CAPG 抑制细胞凋亡和铁死亡，同时通过抑制 P53 途径促进 CRC 细胞增殖。我们的研究表明 CAPG 可能是 CRC 预后和治疗的潜在治疗靶点。