p53正向调控TIMP2并抑制结直肠癌细胞恶性表型

doi:10.3870/j.issn.1672-8009.2026.03.001

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (3): 233-241.doi: 10.3870/j.issn.1672-8009.2026.03.001

• 论著 • 下一篇

p53正向调控TIMP2并抑制结直肠癌细胞恶性表型

袁嘉阳¹, 杜文静^1,2, 李薇¹

¹中国医学科学院北京协和医学院基础医学研究所细胞生物学系北京市,100005
²重大疾病共性机制研究全国重点实验室北京市,100005

收稿日期:2026-03-19 发布日期:2026-06-01
通讯作者: 李薇(E-mail:liwei@ibms.pumc.edu.cn)
基金资助:
国家自然科学基金(No.82303260),中国医学科学院医学与健康科技创新工程(No.2025-I2M-XHJC-018、No.2025-I2M-XHXX-066)

p53 Positively Regulates TIMP2 and Suppresses Malignant Phenotypes of Colorectal Cancer Cells

YUAN Jiayang¹, DU Wenjing^1,2, LI Wei¹

¹Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine PUMC,Beijing,100005,China
²State Key Laboratory of Common Mechanism Research for Major Diseases,Beijing,100005,China

Received:2026-03-19 Published:2026-06-01
Contact: LI Wei(E-mail:liwei@ibms.pumc.edu.cn)
Supported by:
National Natural Science Foundation of China(No.82303260)and the Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences(No.2025-I2M-XHJC-018,No.2025-I2M-XHXX-066)

摘要/Abstract

摘要： 目的探讨p53对金属蛋白酶组织抑制因子2(tissue inhibitor of metalloproteinases 2,TIMP2)的转录调控作用及其对结直肠癌细胞生物学功能的作用。方法采用p53缺失HCT116细胞转录组数据筛选差异表达基因;选取HCT116与HCT8两类结直肠癌细胞株,在p53敲降及激活条件下利用qRT-PCR与蛋白质印迹测定p53对TIMP2的转录调控效应;结合JASPAR数据库与双荧光素酶报告实验,验证p53直接转录调控TIMP2;利用划痕和Transwell实验检测p53过表达与TIMP2缺失对肿瘤细胞迁移和侵袭的作用;利用TCGA数据库分析结直肠癌(TCGA-COAD)中癌与癌旁组织中TIMP2的表达并进行生存情况分析。结果 RNA-seq分析显示TIMP2为差异表达较显著的基因之一;在HCT116与HCT8细胞中TIMP2 mRNA和蛋白质水平均与p53呈正相关;p53可直接转录激活TIMP2,进而抑制肿瘤的恶性表型。TCGA数据库显示COAD肿瘤中TIMP2低表达,且与结直肠癌患者预后较差相关。结论 TIMP2在结直肠癌细胞中低表达,p53部分通过转录调控TIMP2抑制肿瘤细胞转移,表明TIMP2有望成为未来治疗结直肠癌的潜在靶点之一。

关键词: p53, 金属蛋白酶组织抑制因子2, 结直肠癌, 转录调控, 侵袭

Abstract: Objective To explore the transcriptional regulatory effect of p53 on tissue inhibitor of metalloproteinases 2(TIMP2)and its role in the biological functions of colorectal cancer cells. Methods Differentially expressed genes were screened using transcriptome data of p53-deficient HCT116 cells.Two colorectal cancer cell lines,HCT116 and HCT8,were selected,and the transcriptional regulatory effect of p53 on TIMP2 was measured by qRT-PCR and Western blotting under p53 knockdown and activation conditions.The direct transcriptional regulation of TIMP2 by p53 was verified via combining the JASPAR database and dual-luciferase reporter assay.The cell scratch and Transwell assays were used to detect the effects of p53 overexpression and TIMP2 depletion on tumor cell migration and invasion.The TCGA database was used to analyze TIMP2 expression and survival in cancer and adjacent normal tissues in colorectal cancer(TCGA-COAD). Results RNA-seq analysis showed TIMP2 was among the significantly differentially expressed genes.In HCT116 and HCT8 cells,TIMP2 mRNA and protein levels were positively correlated with p53.p53 could directly activate TIMP2 transcription,thereby suppressing tumor malignant phenotypes.The TCGA database showed low TIMP2 expression in COAD tumors,which was associated with poor prognosis in colorectal cancer patients. Conclusion TIMP2 is lowly expressed in colorectal cancer cells,and p53 partially inhibits tumor cell metastasis by transcriptionally regulating TIMP2,indicating that TIMP2 is expected to become a potential target for the future treatment of colorectal cancer.

Key words: p53, tissue inhibitor of metalloproteinases 2, colorectal cancer, transcriptional regulation, invasion

中图分类号:

Q28
R735

袁嘉阳, 杜文静, 李薇. p53正向调控TIMP2并抑制结直肠癌细胞恶性表型[J]. 医学分子生物学杂志, 2026, 23(3): 233-241.

YUAN Jiayang, DU Wenjing, LI Wei. p53 Positively Regulates TIMP2 and Suppresses Malignant Phenotypes of Colorectal Cancer Cells[J]. Journal of Medical Molecular Biology, 2026, 23(3): 233-241.

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p53正向调控TIMP2并抑制结直肠癌细胞恶性表型

p53 Positively Regulates TIMP2 and Suppresses Malignant Phenotypes of Colorectal Cancer Cells

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