| 引用本文: | 余泽豪,莫崇德,侯奇燕,赵洁华,唐毅,张秋环.CBX2通过上调EphA3激活PI3K/AKT/mTOR通路促进结直肠癌进展及5-FU耐药[J].中国临床新医学,,():-. |
| Yu Zehao,Mo Chongde,Hou Qiyan,Zhao Jiehua,Tang Yi.CBX2通过上调EphA3激活PI3K/AKT/mTOR通路促进结直肠癌进展及5-FU耐药[J].中国临床新医学,,():-. |
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| 摘要: |
| 目的:探究染色质盒蛋白2(CBX2)在结直肠癌(CRC)进展及5-FU耐药中的作用机制。方法:利用数据库及临床数据分析CBX2在CRC中的表达、与临床病理特征的关系及对患者预后的影响；通过免疫组化、WB及qRT-PCR检测CRC样本中CBX2表达；构建CBX2下调及过表达细胞模型并通过CCK-8、细胞增殖、Transwell实验评价其对CRC增殖、迁移、侵袭及对5-FU敏感性的影响；利用生信分析并通过细胞实验检验CRC中CBX2对EphA3/PI3K/AKT/mTOR通路的调控作用,以及对CRC生物学行为与对5-FU敏感性的影响。动物实验检验CBX2对CRC细胞体内成瘤能力的影响。结果:CBX2在CRC组织中显著高表达,与肿瘤分化程度、淋巴结转移等相关,是预后不良的独立危险因素。下调CBX2抑制CRC细胞增殖、迁移、侵袭并增强对5-FU敏感性；过表达CBX2则相反。CBX2可上调EphA3并与其直接结合,下调CBX2可降低EphA3表达并抑制 PI3K/AKT/mTOR通路,抑制CRC细胞增殖、迁移、侵袭及对5-FU敏感性。CBX2促进裸鼠CRC细胞体内成瘤。结论:CBX2通过上调EphA3蛋白激活PI3K/AKT/mTOR通路促进CRC进展及5-FU耐药,是CRC治疗的潜在靶点；同时可作为CRC预后及化疗敏感性预测的潜在标志物。 |
| 关键词: 结直肠癌 染色质盒蛋白2 人肝配蛋白A受体-3 5-氟尿嘧啶 化疗 |
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| 基金项目:广西自然科学基金(编号:2023GXNSFBA026003)；广西壮族自治区卫生健康委员会自筹经费科研课题(编号:Z-A20220003) |
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| CBX2 promotes colorectal cancer progression and 5-FU resistance by upregulating EphA3 to activate the PI3K/AKT/mTOR pathway |
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Yu Zehao1,2,3, Mo Chongde, Hou Qiyan, Zhao Jiehua, Tang Yi
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1.Guangxi Zhuang Autonomous Region People'2.'3.s Hospita
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| Abstract: |
| Objective ?To investigate the role of Chromatin Box Protein 2 (CBX2) in colorectal cancer (CRC) progression and 5-FU resistance. Methods? Database and clinical data were analyzed to examine CBX2 expression in CRC, its association with clinical-pathological features, and its impact on patient prognosis. CBX2 expression in CRC samples was detected via immunohistochemistry, Western blotting, and qRT-PCR. Established CBX2 knockdown and overexpression cell models to evaluate their effects on CRC proliferation, migration, invasion, and 5-FU sensitivity via CCK-8 assays, cell proliferation tests, and Transwell experiments. Employed bioinformatics analysis and validated through cellular experiments to investigate CBX2"s regulation of the EphA3/PI3K/AKT/mTOR pathway in CRC, as well as its influence on CRC biological behavior and 5-FU sensitivity. Animal experiments examined CBX2"s impact on CRC cell tumorigenicity in vivo. Results ?CBX2 was significantly overexpressed in CRC tissues, correlated with tumor differentiation grade and lymph node metastasis, and served as an independent prognostic risk factor. Downregulating CBX2 inhibited CRC cell proliferation, migration, and invasion while enhancing 5-FU sensitivity; CBX2 overexpression produced opposite effects. CBX2 upregulates EphA3 through direct binding. Downregulating CBX2 reduces EphA3 expression and inhibits the PI3K/AKT/mTOR pathway, thereby suppressing CRC cell proliferation, migration, invasion, and enhancing 5-FU sensitivity. CBX2 promotes CRC tumorigenesis in nude mice. Conclusion CBX2 promotes CRC progression and 5-FU resistance by activating the PI3K/AKT/mTOR pathway through EphA3 protein upregulation. It represents a potential therapeutic target for CRC and may serve as a prognostic and chemoresponsiveness biomarker. |
| Key words: Colorectal cancer CBX2 EphA3 5-FU Chemotherapy |
