基础医学与临床 ›› 2026, Vol. 46 ›› Issue (8): 1051-1058.doi: 10.16352/j.issn.1001-6325.2026.08.1051

• 研究论文 • 上一篇    下一篇

过表达组蛋白去乙酰化酶4抑制人结直肠癌细胞系的增殖及侵袭

刘获晞#, 黄柏添#, 赵云焘, 张家洋, 吴文梅*   

  1. 广东药科大学 生命科学与生物制药学院,广东 广州 510006
  • 收稿日期:2025-05-21 修回日期:2025-09-24 出版日期:2026-08-05 发布日期:2026-07-22
  • 通讯作者: *wuwenmei@gdpu.edu.cn
  • 作者简介:#对本文有相同贡献
  • 基金资助:
    国家自然科学基金青年项目(32400410);广东省中医药科研项目(20251216);广东省大学生创新创业训练项目(S202510573010)

Overexpression of histone deacetylase 4 inhibits proliferation and invasion of colorectal cancer cells

LIU Huoxi#, HUANG Botian#, ZHAO Yuntao, ZHANG Jiayang, WU Wenmei*   

  1. School of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou 510006, China
  • Received:2025-05-21 Revised:2025-09-24 Online:2026-08-05 Published:2026-07-22
  • Contact: *wuwenmei@gdpu.edu.cn

摘要: 目的 研究过表达组蛋白去乙酰化酶4(HDAC4)对人结直肠癌细胞系的增殖和侵袭影响。方法 基于TCGA、GTEx和HPA公共数据库分析HDAC4在人结直肠癌中的表达水平及其与患者预后的相关性;慢病毒感染技术构建稳定过表达组蛋白去乙酰化酶4的人结直肠癌细胞系SW480和HCT116,利用RT-qPCR和Western blot验证感染效率;CCK-8、EdU、细胞集落形成和Transwell等检测过表达HDAC4对人结直肠癌细胞系的增殖和侵袭作用。结果 数据库分析显示HDAC4在人结直肠癌组织中显著低表达,与患者不良预后密切相关,且HPA临床免疫组化样本验证进一步证实HDAC4在结直肠癌组织中的表达水平显著低于正常结直肠组织;RT-qPCR及Western blot实验结果显示成功构建稳定过表达HDAC4的人结直肠癌细胞系SW480和HCT116;过表达HDAC4降低人结直肠癌细胞的活力(P<0.001)、阳性细胞数(P<0.01)、集落形成数(P<0.001);增殖相关基因PCNA(P<0.01)和MK167(P<0.01)显著下调;此外,过表达HDAC4使人结直肠癌细胞系的侵袭能力减弱(P<0.001)。结论 过表达HDAC4能够抑制人结直肠癌细胞系的增殖和侵袭,为人结直肠癌的精准治疗提供了新的理论支持和实验依据。

关键词: 人结直肠癌, 组蛋白去乙酰化酶4, 细胞增殖和侵袭, 生物标记物

Abstract: Objective To investigate the regulatory role of histone deacetylase 4(HDAC4) overexpression in the proliferation and invasion of human colorectal cancer (CRC) cells. Methods The expression level of HDAC4 in CRC and its correlation with patient prognosis were analyzed using TCGA, GTEx, and HPA databases. Lentiviral transfection was used to construct HDAC4 overexpressing CRC cell lines (SW480 and HCT116), with transfection efficiency verified by RT-qPCR and Western blot. The effects of HDAC4 overexpression on CRC cell proliferation and invasion were assessed using CCK-8, EdU, colony formation, and Transwell assays. Results Database analysis revealed that HDAC4 was significantly downregulated in human CRC tissues and closely associated with poor patient prognosis. Immunohistochemical validation using HPA clinical samples further confirmed that HDAC4 expression was markedly lower in CRC tissues compared to normal colorectal tissues. RT-qPCR and Western blot confirmed the successful establishment of stable HDAC4 overexpressing SW480 and HCT116 cells. HDAC4 overexpression reduced CRC cell viability (P<0.001), decreased the number of EdU-positive cells (P<0.01), and significantly inhibited colony formation (P<0.001). Additionally, HDAC4 overexpression downregulated the expression of proliferation-related genes PCNA(P<0.01) and MK167(P<0.01) and significantly impaired cell invasion ability. Conclusions HDAC4 overexpression suppresses the proliferation and invasion of human CRC cells, providing new theoretical and experimental support for precision therapy in colorectal cancer.

Key words: colorectal cancer, histone deacetylase 4, cell proliferation and invasion, biomarker

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