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Updated: Jun 4, 2025

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
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Published on: April 6, 2012

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

Pankhuri Kaushik1, Radha Mishra1, Champaka Gopal2

  • 1Department of Developmental Biology and Genetics, Indian Institute of Science, Bangalore, India.

Frontiers in Oncology
|December 19, 2024
PubMed
Abstract

Insights

MicroRNA-198 (miR-198) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). Epigenetic silencing of miR-198 promotes OSCC growth by upregulating TOPORS, suggesting miR-198 as a potential therapeutic agent.

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.
Keywords:
MIR198 promoterMiR-198OSCCTOPORSmethylationtumor suppressor

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