Epigenetic regulation of the SPARC gene in bladder cancer

Bladder cancer is the most commonly diagnosed malignancy that affects the urinary system, with an estimated 82,290 new cases and 16,710 deaths in 2023 alone, according to the NCI bladder cancer page. A gene called SPARC (Secreted Protein Acidic and Rich in Cysteine), which encodes an extracellular matrix protein that regulates cell-cell and cell-matrix interactions, has been implicated in the progression of bladder cancer cells into more aggressive forms. Little is known about how SPARC is regulated in bladder cancer, although some prior work in other cancers suggests epigenetics might play a role. We investigated potential mechanisms regulating SPARC gene expression, including non-coding RNA, DNA methylation, and transcription factors. We found that while DNA methylation is inversely correlated with SPARC expression, it does not fully account for differences in expression. Next, we found that expression of the non-coding RNA CLMAT3 is oppositely correlated with SPARC but does not appear to regulate SPARC expression in trans. Lastly, we sought to determine which transcription factors might work to regulate SPARC expression.