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JARID1B-Mediated H3K4me3 Demethylation Promotes Cisplatin Resistance in Oral Squamous Cell Carcinoma Cells via the
1Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Abstract:
Cisplatin (DDP) is a commonly used chemotherapeutic drug for oral squamous cell carcinoma (OSCC) clinical treatment. However, DDP resistance often brings about treatment failure. This study aims to demonstrate the mechanism of JARID1B in DDP-resistance of OSCC cells. Tissue specimens of OSCC and adjacent normal tissues were collected and OSCC cell lines resistant to DDP were established, followed by measurement of JARID1B, H3K4me3, miR-495-3p and FUBP1 levels. CCK-8 was used to detect the IC50 value. Cell proliferation and apoptosis were assayed. The enrichment of JARID1B and H3K4me3 on the miR-495-3p promoter was assayed via ChIP. The binding between miR-495-3p and FUBP1 was confirmed via dual-luciferase reporter assay. Results showed that JARID1B and FUBP1 were highly expressed in OSCC, while miR-495-3p was lowly expressed. After inhibiting JARID1B expression in OSCC cells, cell proliferation was decreased, apoptosis was increased, and cell resistance to DDP was reduced. JARID1B downregulation increased H3K4me3 levels and promoted miR-495-3p expression, which promoted the binding of miR-495-3p to FUBP1, thus downregulating FUBP1 transcription. FUBP1 overexpression or miR-495-3p downregulation partially reversed the inhibitory effect of JARID1B downregulation on DDP resistance of OSCC cells. In conclusion, JARID1B-mediated H3K4me3 demethylation promotes DDP resistance in OSCC cells through the miR-495-3p/FUBP1 axis.
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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