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MicroRNA 452 regulates IL20RA-mediated JAK1/STAT3 pathway in inflammatory colitis and colorectal cancer

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Abstract

Objective

MicroRNAs are a class of small, non-coding RNAs that play a key role in several biological and molecular processes, including tumorigenesis. We previously identified that MIR452 is upregulated in both colorectal cancer (CRC) and colitis. However, the functional mechanisms of MIR452 and its target genes in CRC and colitis are not well understood. So, we hypothesize that MIR452 can influence CRC and DSS-induced colitis model through the regulation of IL20RA and its downstream JAK-STATs signaling pathway.

Methods

We used a luciferase reporter assay to confirm the effect of MIR452 on IL20RA expression. The protein and mRNA expression of a target gene and its associated molecules were measured by western blot, quantitative RT-PCR, and immunohistochemistry.

Results

We found that the IL20RA was a direct target gene of MIR452. Overexpression of MIR452 in CRC cell lines significantly decreased IL20RA and its downstream Janus kinase 1 (JAK1), Signal transducer and activator of transcription 1 (STAT1) and STAT3. Knockdown of IL20RA in CRC cell lines by IL20RA gene silencing also decreased the expression of IL20RA, JAK1, and STAT3, but not of STAT1.

Conclusion

Our results suggest that MIR452 regulates STAT3 through the IL20RA-mediated JAK1 pathway, but not STAT1. Overall, MIR452 acts as tumor suppressor in human CRC and in a mouse colitis model. These findings suggest that MIR452 is a promising therapeutic target in the treatment of cancer and colitis.

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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 2020.

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Author notes

  1. Santosh Lamichhane and Ji-Su Mo contributed equally to this work.

Authors and Affiliations

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

    Santosh Lamichhane, Grinsun Sharma, Tae-Young Choi & Soo-Cheon Chae

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

    Ji-Su Mo & Soo-Cheon Chae

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  1. Santosh Lamichhane
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  2. Ji-Su Mo
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Contributions

The authors have made the following declarations about their contributions: Conceived and designed the experiments: SCC. Performed the experiments, analyzed the data and discussion: SL, JSM, GS, and SCC. Contributed to draft and revision of the manuscript: SL, TYC and SCC.

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Correspondence to Soo-Cheon Chae.

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The authors declare that they have no conflict of interest.

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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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Lamichhane, S., Mo, JS., Sharma, G. et al. MicroRNA 452 regulates IL20RA-mediated JAK1/STAT3 pathway in inflammatory colitis and colorectal cancer. Inflamm. Res. 70, 903–914 (2021). https://doi.org/10.1007/s00011-021-01486-7

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  • DOI: https://doi.org/10.1007/s00011-021-01486-7

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