Oxymatrine suppresses oral squamous cell carcinoma progression by suppressing CXC chemokine receptor 4 in an m<sup>6</sup>A modification decrease dependent manner

Luo,Renhui; Xie,Lili; Lin,Yingmei; Shao,Jun; Lin,Zhejing

doi:10.3892/or.2022.8392

October-2022 Volume 48 Issue 4

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October-2022 Volume 48 Issue 4

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Article

Oxymatrine suppresses oral squamous cell carcinoma progression by suppressing CXC chemokine receptor 4 in an m⁶A modification decrease dependent manner

Authors:
- Renhui Luo
- Lili Xie
- Yingmei Lin
- Jun Shao
- Zhejing Lin
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Affiliations: Department of Stomatology, Guangzhou Hospital of Integrated Traditional and West Medicine, Guangzhou, Guangdong 510800, P.R. China, Department of Stomatology, Hainan General Hospital, Haikou, Hainan 570102, P.R. China, Department of Stomatology, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, Guangdong 518034, P.R. China
Article Number: 177
|
Published online on: August 23, 2022

https://doi.org/10.3892/or.2022.8392
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Abstract

Oxymatrine has been revealed to exert antitumor activity; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. In the present study, the effects and underlying molecular mechanisms of oxymatrine in OSCC were explored. The antineoplastic effects of oxymatrine were measured using Cell Counting Kit‑8, apoptosis and Transwell assays. The inhibitory effect of oxymatrine on tumor growth was evaluated in vivo. The regulation of oxymatrine on the CXC chemokine receptor 4 (CXCR4) was analyzed using western blotting, reverse transcription‑quantitative PCR, RNA stability and methylated RNA immunoprecipitation assays. The present results revealed that oxymatrine inhibited the proliferation and migration of OSCC cells and promoted cell apoptosis. Furthermore, oxymatrine reduced CXCR4 mRNA and protein expression levels by promoting CXCR4 mRNA degradation. Mechanistically, oxymatrine inhibited the methylation at the N6‑position of adenosine (m⁶A modification) of CXCR4 mRNA by decreasing the expression of the methyltransferase‑like 3 (METTL3) gene. In addition, oxymatrine inhibited tumor growth in vivo. Taken together, our findings demonstrated the antitumor effect of oxymatrine on OSCC. Mechanistically, oxymatrine inhibited the progression of OSCC by downregulating METTL3 and degrading CXCR4 mRNA by decreasing the level of m⁶A modification.

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