The role of myoglobin in epithelial cancers - insights from transcriptomic. Transcriptome analyses of MB knockdown cancer cell lines

The muscle-associated respiratory protein myoglobin (MB) is expressed in multiple cancers, including breast and prostate tumors. In both entities, Kaplan-Meier analyses correlate MB positivity with favorable prognoses. Despite its well-characterized function in myocytes, the role of MB in cancer remains unclear. To study the impact of endogenous MB expression, we engineered siRNA MB-knockdowns in breast, prostate and colon cancer cell lines (MDA-MB468, LNCaP, DLD-1) and investigated their transcriptomes using RNA-Seq at different oxygen levels. In MB-proficient cells, increased expression of glycolytic genes was observed, possibly mediated by a higher activity of HIF1α. In addition, gene-set enrichment data suggest that MB contributed to the transport and turnover of fatty acids. MB-positive, wildtype-p53 LNCaP cells further showed increased expression of p53 target genes involved in cell cycle checkpoint control and prevention of cell migration. MB-proficient cells that express mutant p53 showed upregulation of genes associated with prolonged cancer cell viability and motility. We hypothesize that these transcriptomic differences could result from an MB-mediated generation of NO· or ROS, thus employing established enzymatic activities of the globin. In summary, the transcriptome comparisons pinpoint possible molecular functions of MB in carcinogenesis by highlighting the interplay of MB with key metabolic and regulatory processes.