医学分子生物学杂志2026，Vol.23Issue(3)：233-241,9.DOI:10.3870/j.issn.1672-8009.2026.03.001
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
摘要
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-defi-cient 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 deple-tion 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,indica-ting that TIMP2 is expected to become a potential target for the future treatment of colorectal cancer.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Key words
p53/tissue inhibitor of metalloproteinases 2/colorectal cancer/transcriptional regulation/invasion分类
生物科学引用本文复制引用
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):233-241,9.基金项目
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) This work was supported by grants from the National Natural Science Foundation of China(No.82303260)and the Medical and Health Technology Inno-vation Project of the Chinese Academy of Medical Sciences(No.2025-I2M-XHJC-018,No.2025-I2M-XHXX-066). （No.82303260）
