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

Renhui Luo1, Lili Xie2, Yingmei Lin1

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Oncology Reports
|August 25, 2022
PubMed
Summary

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.

Keywords:
CXCR4METTL3OSCCm6Aoxymatrine

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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.