Abstract
Background
In a previous study, we found that the expression of microRNA 429 (MIR429) was decreased in dextran sodium sulfate (DSS)-induced mouse colitis tissues.
Objective
In this study, we aimed to investigate the interaction of MIR429 with TIMP metallopeptidase inhibitor 2 (TIMP2), one of its candidate target genes, in human colorectal cancer (CRC) cells and DSS-induced mouse colitis tissues.
Methods
A luciferase reporter system was used to confirm the effect of MIR429 on TIMP2 expression. The expression levels of MIR429 and target genes in cells or tissues were evaluated through quantitative RT-PCR, western blotting, or immunohistochemistry.
Results
We found that the expression level of MIR429 was downregulated in human CRC tissues, and also showed that TIMP2 is a direct target gene of MIR429 in CRC cell lines. Furthermore, MIR429 regulate TIMP2-mediated matrix metallopeptidases (MMPs) expression in CRC cells. We also generated cell lines stably expressing MIR429 in CRC cell lines and showed that MIR429 regulates the expression of MMPs by mediating TIMP2 expression. In addition to human CRC tissues, we found that TIMP2 was highly expressed in mouse colitis tissues and human ulcerative colitis (UC) tissues.
Conclusions
Our findings suggest that the expression of endogenous MIR429 was reduced in human CRC tissues and colitis, leading to upregulation of its target gene TIMP2. The upregulation of TIMP2 by decreased MIR429 expression in CRC tissues and inflamed tissues suggests that it may affect extracellular matrix (ECM) remodeling through downregulation of MMPs. Therefore, MIR429 may have therapeutic value for human CRC and colitis.
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Data Availability
All data generated or analyzed during this study are included in this published article.
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Acknowledgements
The biospecimens for this study were provided by the Biobank of Wonkwang University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare. This research was supported by Wonkwang University in 2022.
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This research was supported by Wonkwang University in 2022.
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The authors declared the following for their respective contributions: SC Chae: conceived and designed the experiments and contributed to the writing of the manuscript; SH Han and JS Mo: performed the experiments, analyzed the data; KJ Yun: contributed reagents/materials and discussion. All authors reviewed the manuscript.
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All procedures performed in studies involving humans were in accordance with the Ethical Standards set by the Committee of Ethical Standards of Wonkwang University, Republic of Korea (WKIRB-201703-BR-011). The animal studies were approved by the Animal Care Committee of the Wonkwang University (WKU17-53).
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Han, SH., Mo, JS., Yun, KJ. et al. MicroRNA 429 regulates MMPs expression by modulating TIMP2 expression in colon cancer cells and inflammatory colitis. Genes Genom (2024). https://doi.org/10.1007/s13258-024-01520-y
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DOI: https://doi.org/10.1007/s13258-024-01520-y