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Published on: December 13, 2018
Oxymatrine suppresses oral squamous cell carcinoma progression by suppressing CXC chemokine receptor 4 in an m6A
Renhui Luo1, Lili Xie2, Yingmei Lin1
1Department of Stomatology, Guangzhou Hospital of Integrated Traditional and West Medicine, Guangzhou, Guangdong 510800, P.R. China.
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.
Insights
Oxymatrine demonstrates antitumor effects against oral squamous cell carcinoma (OSCC). It inhibits cancer progression by reducing METTL3, degrading CXCR4 mRNA, and decreasing m6A modification, ultimately suppressing tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Oral squamous cell carcinoma (OSCC) is a significant global health concern.
- Oxymatrine, a natural compound, exhibits potential antitumor properties, but its specific role in OSCC requires elucidation.
Purpose of the Study:
- To investigate the antitumor effects of oxymatrine in OSCC.
- To explore the underlying molecular mechanisms, focusing on the regulation of CXC chemokine receptor 4 (CXCR4) and its associated modifications.
Main Methods:
- Cell Counting Kit-8, apoptosis, and Transwell assays were used to assess antineoplastic effects in vitro.
- In vivo tumor growth inhibition was evaluated.
- Western blotting, RT-qPCR, RNA stability, and methylated RNA immunoprecipitation assays were employed to analyze CXCR4 regulation and m6A modification.
Main Results:
- Oxymatrine significantly inhibited OSCC cell proliferation and migration while promoting apoptosis.
- Oxymatrine reduced both CXCR4 mRNA and protein levels by enhancing mRNA degradation.
- The compound decreased m6A modification of CXCR4 mRNA by downregulating methyltransferase-like 3 (METTL3) expression, leading to reduced tumor growth in vivo.
Conclusions:
- Oxymatrine exhibits significant antitumor activity against OSCC.
- The mechanism involves the downregulation of METTL3, leading to decreased m6A modification of CXCR4 mRNA, subsequent degradation, and inhibition of OSCC progression and tumor growth.
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