miR-198 targets TOPORS: implications for oral squamous cell carcinoma pathogenesis

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• MicroRNAs (miRNAs) are crucial in disease progression, particularly in oral squamous cell carcinoma (OSCC).
• Dysregulation of miRNAs, including epigenetic silencing of tumor suppressors, contributes significantly to OSCC tumorigenesis.
• This study investigates the tumor-suppressive function of miR-198 in OSCC.

Purpose of the Study:

• To explore the tumor suppressive role of miR-198 in oral squamous cell carcinoma (OSCC).
• To investigate the epigenetic regulation of miR-198 and its downstream targets in OSCC.
• To evaluate the therapeutic potential of miR-198 in OSCC.

Main Methods:

• miRNA analysis in OSCC cell lines, patient samples, and xenograft models.
• Bioinformatics, qRT-PCR, dual-luciferase reporter assays, and Western blotting to study miR-198 and TOPORS interaction.
• Bisulfite sequencing PCR to confirm promoter methylation of MIR198.

Main Results:

• miR-198 is epigenetically silenced in OSCC, with promoter hypermethylation confirmed.
• TOPORS identified as a novel direct target of miR-198.
• miR-198 represses TOPORS, decreasing cell proliferation and enhancing apoptosis in OSCC cells.
• Synthetic miR-198 mimic significantly reduced tumor size in a xenograft mouse model.

Conclusions:

• Epigenetic silencing of miR-198 in OSCC promotes tumor growth, partly via TOPORS upregulation.
• miR-198 exhibits tumor-suppressive activity in OSCC.
• miR-198 holds therapeutic potential for OSCC treatment.