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MicroRNA 452 regulates SHC1 expression in human colorectal cancer and colitis

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Abstract

Background

Human microRNA 452 (MIR452) has been linked to both colorectal cancer (CRC) tissues and dextran sulfate sodium (DSS)-induced colitis.

Objective

We analyzed the correlation between MIR452 and its putative target gene in human CRC cells and in mouse colitis tissues.

Methods

Luciferase reporter assay confirmed that Src homologous and collagen adaptor protein 1 (SHC1) is a direct target of MIR452. Furthermore, the expression of proteins or mRNA was assessed by immunohistochemical analysis, Western blot, or quantitative RT-PCR (qRT-PCR).

Results

We found that MIR452 has a potential binding site at 3′-UTR of SHC1. Likewise, MIR452 or siSHC1 transfection dramatically reduced the level of cellular SHC1 in CRC cells. The expression of SHC1 was frequently downregulated in both human CRC tissues and mouse colitis tissues. In CRC cells, we demonstrated that MIR452 regulated the expression of genes involved in the SHC1-mediated KRAS-MAPK signal transduction pathways.

Conclusion

These findings suggest a potential defense mechanism in which MIR452 regulation of the adaptor protein SHC1 maintains cellular homeostasis during carcinogenesis or chronic inflammation. Therefore, MIR452 may have therapeutic value for human early-stage CRC and colitis.

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Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

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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 2021.

Funding

This research was supported by Wonkwang University in 2021.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea

    Ji-su Mo, Santosh Lamichhane, Ki-jung Yun & Soo-Cheon Chae

  2. Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea

    Ji-su Mo & Soo-Cheon Chae

  3. Department of Genetics, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Santosh Lamichhane

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  1. Ji-su Mo
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Contributions

The authors confirm contribution and declaration to the paper are as follows: Study concepts, design, draft the manuscript, and revised it critically: S-CC. Performed the experiments, data collection, interpretation and analysis of results: J-SM and S-CC. Contributed reagents/materials and discussion: SL and K-JY.

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Correspondence to Soo-Cheon Chae.

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The authors have no conflict of interest to disclose.

Ethical approval

All procedures involving human subjects were examined and endorsed in accordance with the Ethical Standards set by the Committee of Ethical Standards of Wonkwang University, Republic of Korea (WKIRB-201703-BR-010). The consent for the animal experiments was approved by the Institutional Animal Care and Use Committee (WKU17-53).

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Mo, Js., Lamichhane, S., Yun, Kj. et al. MicroRNA 452 regulates SHC1 expression in human colorectal cancer and colitis. Genes Genom 45, 1295–1304 (2023). https://doi.org/10.1007/s13258-023-01432-3

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  • DOI: https://doi.org/10.1007/s13258-023-01432-3

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