Dose-dependent activation of putative oncogene SBSN by BORIS

Area of Science:

• Epigenetics
• Molecular Biology
• Cancer Research

Background:

• Brother of the Regulator of Imprinted Sites (BORIS) is a testis-specific transcription factor abnormally expressed in various cancers.
• BORIS is implicated in the epigenetic activation of cancer-testis antigens (CTAs).
• Suprabasin (SBSN), normally restricted to epidermis, is epigenetically derepressed in lung cancer.

Purpose of the Study:

• To establish suprabasin (SBSN) as a novel non-CTA target of BORIS epigenetic regulation.
• To investigate the role of BORIS dosage in SBSN gene expression and cellular behavior.

Main Methods:

• Utilized a doxycycline-inducible BORIS expressing vector in the H358 human lung cancer cell line.
• Analyzed SBSN CpG island methylation and chromatin structure around the transcription start site (TSS).
• Assessed the impact of varying BORIS concentrations on SBSN expression, cell growth, and colony formation.

Main Results:

• Lower BORIS concentrations induced SBSN CpG island demethylation and chromatin activation, increasing SBSN expression 35-fold.
• Higher BORIS concentrations led to reduced SBSN expression through chromatin repression.
• Increased BORIS concentrations also inhibited cell growth and colony formation.

Conclusions:

• This study demonstrates that BORIS epigenetically regulates suprabasin (SBSN) as a novel non-CTA target.
• BORIS dosage is critical in determining its effects on target gene expression and cellular processes via chromatin remodeling.
• The findings highlight a dose-dependent, dual role of BORIS in gene regulation and cancer cell proliferation.