JARID1B-Mediated H3K4me3 Demethylation Promotes Cisplatin Resistance in Oral Squamous Cell Carcinoma Cells via the

Jixiong Mao1, Lei Xu2

  • 1Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

Insights

JARID1B promotes cisplatin resistance in oral squamous cell carcinoma (OSCC) by downregulating miR-495-3p and upregulating FUBP1. Inhibiting JARID1B may reverse this resistance, offering a potential therapeutic strategy for OSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Cisplatin (DDP) is a cornerstone chemotherapy for oral squamous cell carcinoma (OSCC).
  • Acquired DDP resistance in OSCC cells significantly limits treatment efficacy and patient outcomes.
  • Understanding the molecular mechanisms underlying DDP resistance is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To elucidate the role and mechanism of JARID1B in mediating DDP resistance in OSCC.
  • To investigate the molecular axis involving JARID1B, H3K4me3, miR-495-3p, and FUBP1 in OSCC DDP resistance.

Main Methods:

  • Collected OSCC and adjacent normal tissue specimens; established DDP-resistant OSCC cell lines.
  • Quantified JARID1B, H3K4me3, miR-495-3p, and FUBP1 expression levels.
  • Assessed cell viability (CCK-8), proliferation, apoptosis, and performed ChIP and dual-luciferase reporter assays.

Main Results:

  • JARID1B and FUBP1 were upregulated, while miR-495-3p was downregulated in OSCC.
  • JARID1B inhibition decreased proliferation, increased apoptosis, and reduced DDP resistance in OSCC cells.
  • JARID1B downregulation increased H3K4me3 and miR-495-3p, leading to FUBP1 downregulation via miR-495-3p binding.

Conclusions:

  • JARID1B promotes DDP resistance in OSCC cells through epigenetic regulation of the miR-495-3p/FUBP1 axis.
  • Targeting JARID1B-mediated H3K4me3 demethylation offers a potential therapeutic avenue to overcome DDP resistance in OSCC.

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