Expression analysis of androglobin and its influence on the transcriptome in cancer

Androglobin (ADGB) is a phylogenetically ancient multi-domain protein with an embedded globin domain, which binds heme and may therefore interact with gaseous molecules. Other globins like neuroglobin, cytoglobin and myoglobin have shown tumor-suppressor or oncogenic roles in a tissue-dependent way, and also ADGB has been suggested as being oncogenic in prostate and brain cancer models. However, ADGB expression in human tumor entities in vivo has not been investigated systematically so far. Here we mined transcriptome data from various cancer types and reveal that ADGB is typically downregulated in cancer cell lines, as well as in tumors from lung and testis, which express ADGB endogenously in healthy states. We show via bioinformatics analyses that in cell lines only a few ADGB exons are transcribed, or the gene locus was amplified, which greatly limits suitability of such cell lines as model systems for research into ADGB. Consistent with correlation analysis, we further demonstrate that RFX3 regulates ADGB promoter-driven luciferase activity as well as endogenous ADGB expression levels. Since recent literature postulated oncogenic effects of ADGB, we established stable ADGB overexpression (ADGB+) in A549 lung cancer cells. Our transcriptomic analysis of ADGB + cells indicate increased cell motility and restructuring of the extracellular matrix - both hallmarks of elevated malignancy. ADGB thus may display oncogenic potential in vitro. However, since human cancer entities show little to no ADGB transcription, a role for ADGB in tumorigenesis in vivo appears rather limited.