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Downregulation of the paired box gene 3 inhibits the progression of skin cutaneous melanoma by inhibiting c-MET tyrosine kinase

PAX3 downregulation inhibits melanoma progression

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Abstract

Background

The PAX3 (paired box gene 3) gene is highly expressed in several cancer types. However, its underlying mechanism of action in skin cutaneous melanoma (SKCM) remains unknown.

Methods

In this study, we used the GEPIA database and western blotting to analyze the expression of PAX3. We performed the Kaplan-Meier survival analysis to evaluate the prognostic value of PAX3 in SKCM. Next, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to evaluate the function of PAX3-related co-expressed genes. Additionally, the function and potential mechanism of action of PAX3 in SKCM were studied through functional experiments. Western blotting was used to detect the changes in the levels of epithelial-mesenchymal transition (EMT)-related and MET (c-MET tyrosine kinase) proteins following PAX3 knockdown. Finally, we assessed the correlation between PAX3 expression and the infiltration of CD4+/CD8+ T cells using the TISIDB database.

Results

We found that PAX3 was overexpressed in the SKCM tissues and that these levels were indicative of a poor prognosis of SKCM. The KEGG pathway enrichment analysis showed that PAX3-related co-expressed genes were mainly associated with the oncogenic pathways. Knocking down PAX3 significantly inhibited the proliferation, invasion, and migration of SK-MEL-28 cells. The PAX3 expression was related significantly to the immune infiltration level of CD4+/CD8+ T cells.

Conclusions

Our findings demonstrated that PAX3 knockdown could reverse the EMT of tumor cells, inhibit the growth, and progression of SKCM cells. Therefore, PAX3 may have implications as a potential therapeutic target and promising prognostic biomarker for SKCM.

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Data Availability Statement

Part of the data is derived from the TCGA/GTEX data set and other original data are provided by the author and will not be retained.

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Acknowledgments

We thank Bullet Edits Limited for the linguistic editing and proofreading of our manuscript.

Funding

This research was supported by the Guangxi Provincial Department of Education (2021KY0521).

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Authors and Affiliations

  1. Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, CN, China

    Kun Zhang, Wancong Zhang & Shijie Tang

  2. Department of Nursing, Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, CN, China

    Chunfang Yu

  3. School of Basic Medicine, Tianjin Medical University, Tianjin, CN, China

    Ruoxi Tian

  4. Department of General Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hbei, CN, China

    Guiying Wang

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Contributions

All authors made substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data; aided in drafting the article or revising it critically for important intellectual content; provided final approval of the version to be published; and agreed to be accountable for all aspects of the work.

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Correspondence to Shijie Tang or Guiying Wang.

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This study was approved by the Ethics Committee of the Second Affiliated Hospital of Shantou University Medical College (ethics number: 2021-117). Informed consent was obtained from all patients participating in this study.

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Zhang, K., Yu, C., Tian, R. et al. Downregulation of the paired box gene 3 inhibits the progression of skin cutaneous melanoma by inhibiting c-MET tyrosine kinase. Mol Biol Rep 49, 9137–9145 (2022). https://doi.org/10.1007/s11033-022-07706-5

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