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

doi:10.3870/j.issn.1672-8009.2026.03.001

Abstract

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

CLC Number:

Q28
R735

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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