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WTAP accelerates keloids formation by mediating m6A modification of HOXA5 to suppress p53 pathway

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Abstract

Background

N6-methyladenosine (m6A) modification has been identified to participate in cancer progression. However, the function of m6A modification in keloid, a kind of fibrous benign tumor, is still not fully explored. This study aimed to explore the function and mechanism of a m6A methyltransferase Wilm's tumor 1–associating protein (WTAP) in keloids formation.

Methods

The levels of WTAP and Homeobox A5 (HOXA5) in keloids were confirmed by qRT-PCR or western blotting analysis. The change of human keloid fibroblasts (HKFs) cell function was verified by CCK8, wound healing, and transwell assays. Besides, the m6A modification of HOXA5 caused by WTAP was determined by MeRIP assay.

Results

WTAP was upregulated in keloids, whereas HOXA5 was downregulated in keloids. Upregulating WTAP enhanced the abilities of HKFs proliferation, migration, and invasion, but upregulating HOXA5 showed the opposite effect on HKFs. Moreover, HOXA5 could be mediated the m6A modification by WTAP, and HOXA5 overexpression reversed the promotive effect of WTAP overexpression on HKFs by activating p53 pathway.

Conclusion

WTAP can mediate the m6A modification of HOXA5 to regulate p53 pathway, thereby accelerating keloids formation. Our findings provide new insights into the mechanisms of keloid formation by m6A modification, which may promote the development of targeted therapies for keloids to reduce the recurrence rate.

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This article contains all data that were created or examined during this investigation.

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Funding

Authors did not received any funding for this work.

Author information

Authors and Affiliations

  1. Dermatology Department, Ezhou Central Hospital, Ezhou, 436000, Hubei, China

    Lin Liu & Kun Du

  2. Dermatology Department, Sinopharm Gezhouba Central Hospital, No.60, Qiaohuyi Road, Xiling District, Yichang, 443000, Hubei, China

    Miao Chen

Authors
  1. Lin Liu
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  2. Kun Du
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  3. Miao Chen
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Contributions

Both the experiments and the data analysis were done by LL. KD designed this study. The paper was written and reviewed by LL and MC. All authors evaluated and approved the article.

Corresponding author

Correspondence to Miao Chen.

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According to the authors, there were no conflicts of interest.

Ethical approval

This study was authorized by the ethics committee of Ezhou Central Hospital (Ezhou, China). The Declaration of Helsinki's ethical guidelines were followed in the processing of the clinical tissue samples. A form for informed consent was filled out by each patient. All of the patients completed an informed consent form.

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Liu, L., Du, K. & Chen, M. WTAP accelerates keloids formation by mediating m6A modification of HOXA5 to suppress p53 pathway. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00383-w

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  • DOI: https://doi.org/10.1007/s13273-023-00383-w

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