SET protein modulates H4 histone methylation status and regulates miR-137 level in oral squamous cell carcinoma

Area of Science:

• Molecular Biology
• Epigenetics
• Cancer Research

Background:

• Histone modifications, including acetylation and methylation, are crucial regulators of gene expression.
• Oral squamous cell carcinoma (OSCC) is a prevalent cancer where gene expression dysregulation plays a significant role.

Purpose of the Study:

• To investigate the effect of SET protein knockdown on histone methylation patterns.
• To determine the consequences of altered histone methylation on microRNA (miRNA) levels in OSCC.
• To explore the functional role of miR-137 in OSCC progression.

Main Methods:

• Quantitative real-time PCR was used to measure miRNA levels in OSCC cells.
• Immunoreactions were employed to assess histone modification status.
• SET protein's binding to the miR-137 promoter was analyzed.

Main Results:

• SET knockdown led to increased levels of histone H4K20me2 and miR-137.
• SET protein was found to bind to the miR-137 promoter region.
• Transfection with a miR-137 mimic reduced KI67 and Rb protein levels and decreased OSCC cell proliferation.

Conclusions:

• This study establishes a novel link between SET, histone methylation, and miRNA expression control in OSCC.
• KI67 and Rb proteins are identified as direct targets of miR-137.
• These findings highlight a potential therapeutic pathway involving miR-137 for OSCC treatment.