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Coxsackievirus B3 suppresses oral squamous cell carcinoma by inducing ferroptosis through the
Zhao Bowen1, Li Jianhao1, Li Zhengmiao1
1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, China.
Abstract:
Oral squamous cell carcinoma (OSCC) exhibits aggressive invasion with limited treatment options. This study investigates the oncolytic potential of coxsackievirus B3 (CVB3) against OSCC and explores its ability to induce ferroptosis. Gene Set Enrichment Analysis (GSEA) highlighted CVB3's efficacy in initiating ferroptosis, placing the pathogen as a hopeful option in cancer treatment. We demonstrated CVB3 infection significantly inhibited OSCC cell proliferation and tumor growth in mouse models. Biochemical tests verified ferroptosis activation, marked by increased Fe2+, lipid reactive oxygen species (ROS), and malondialdehyde (MDA) levels, alongside decreased glutathione (GSH). These effects were reversed by ferroptosis inhibitors. Mechanistically, CVB3 downregulated circ_0010074 and its target Glutathione peroxidase 4 (GPX4), while upregulating miR-214-3p. Using fluorescence in situ hybridization (FISH) and luciferase assays, we found circ_0010074 sequesters miR-214-3p to regulate GPX4 expression. Our research demonstrates that CVB3 acts as a highly effective oncolytic virus in targeting OSCC, inducing ferroptosis via the previously unrecognized circ_0010074/miR-214-3p/GPX4 pathway. This discovery opens new doors for treating this particularly aggressive form of cancer, offering a potentially groundbreaking therapeutic approach.
Insights
Coxsackievirus B3 (CVB3) shows promise as an oncolytic virus therapy for oral squamous cell carcinoma (OSCC). It effectively inhibits tumor growth by inducing ferroptosis through a novel molecular pathway.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Oral squamous cell carcinoma (OSCC) is an aggressive cancer with limited therapeutic options.
- Oncolytic viruses are being explored as a novel cancer treatment strategy.
Purpose of the Study:
- To investigate the oncolytic potential of coxsackievirus B3 (CVB3) against OSCC.
- To determine if CVB3 can induce ferroptosis in OSCC cells.
- To elucidate the molecular mechanisms underlying CVB3-induced ferroptosis in OSCC.
Main Methods:
- Gene Set Enrichment Analysis (GSEA) to identify pathways affected by CVB3.
- In vitro cell proliferation assays and in vivo tumor growth studies in mouse models.
- Biochemical assays to measure markers of ferroptosis (Fe2+, lipid ROS, MDA, GSH).
- Molecular techniques including FISH and luciferase assays to investigate gene and microRNA interactions.
Main Results:
- CVB3 infection significantly inhibited OSCC cell proliferation and tumor growth.
- CVB3 induced ferroptosis in OSCC cells, evidenced by increased Fe2+, lipid ROS, MDA, and decreased GSH.
- CVB3 downregulated circ_0010074 and Glutathione peroxidase 4 (GPX4), while upregulating miR-214-3p.
- The circ_0010074/miR-214-3p/GPX4 pathway was identified as a key mechanism for CVB3-induced ferroptosis.
Conclusions:
- CVB3 demonstrates significant oncolytic activity against OSCC.
- CVB3 induces ferroptosis in OSCC cells via the circ_0010074/miR-214-3p/GPX4 pathway.
- This study reveals a novel therapeutic strategy for OSCC using CVB3 and highlights its potential in cancer treatment.
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