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RUNX1/miR-429 feedback loop promotes growth, metastasis, and epithelial-mesenchymal transition in oral squamous cell carcinoma by targeting ITGB1

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Abstract

This study aimed to explore the role of miR-429 on the progression of oral squamous cell carcinoma (OSCC). OSCC cell lines were transfected with miR-429 mimic, pcDNA3.1-RUNX1, or pcDNA3.1-ITGB1, and their cell viability, apoptosis, migration, and invasion abilities were analyzed by cell counting, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, wound healing, and transwell assays, respectively. Furthermore, luciferase reporter assay, RNA pull-down, and ChIP were used to assess the regulation of miR-429, RUNX1, and ITGB1 expression in OSCC. Lastly, the biological role of the RUNX1/miR-429 feedback loop was explored in nude mice. The results revealed that miR-429 level was down-regulated, while RUNX1 and ITGB1 levels were up-regulated in OSCC tissues and that miR-429 was negatively correlated with RUNX1 and ITGB1 in OSCC tissues. Transfection of miR-429 mimic suppressed OSCC cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT). Moreover, we found that miR-429 participated in OSCC progression by directly targeting ITGB1. Additionally, we found that RUNX1 negatively regulated miR-429 expression by binding to its promoter. Our results also revealed that the RUNX1/miR-429 feedback loop regulated ITGB1 expression and that RUNX1 overexpression rescued the inhibitory effects of miR-429 mimic on OSCC cells. In addition, miR-429 mimic significantly suppressed tumor growth, inflammatory cell infiltration, EMT, and ITGB1 expression in vivo, which were inhibited by RUNX1 overexpression. Altogether, these results indicate that the RUNX1/miR-429 feedback loop promoted growth, metastasis, and EMT in OSCC by targeting ITGB1.

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Acknowledgements

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Funding

Ningxia Natural Science Foundation Project Plan (Project number: 2022AAC03565).

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Authors and Affiliations

  1. Hospital of Stomatology, General Hospital of Ningxia Medical University, 804 Shengli South Street, Xingqing District, Yinchuan City, Ningxia, 750004, China

    Xun Lu, Yiqiang Yang, Jia Chen, Tian Zhao & Xiaofan Zhao

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  1. Xun Lu
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  3. Jia Chen
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  4. Tian Zhao
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  5. Xiaofan Zhao
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Contributions

Conceptualisation, XZ, and XL; formal analysis, YY, JC, and TZ; data curation, XZ, YY, JC, and TZ; writing, original draft preparation, XL; writing, review and editing, XZ, and XL; supervision, XZ; project administration, XZ, and XL; and funding acquisition, XZ. All authors have read and agreed to the published version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Xiaofan Zhao.

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The consent agreement was signed by all patients and the project was approved by the Ethics Committee of General Hospital of Ningxia Medical University (Ethics approval number: KYLL-2021-772).

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Lu, X., Yang, Y., Chen, J. et al. RUNX1/miR-429 feedback loop promotes growth, metastasis, and epithelial-mesenchymal transition in oral squamous cell carcinoma by targeting ITGB1. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-02960-9

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