Obstructive sleep apnea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

In patients with obstructive sleep apnea (OSA), intermittent hypoxia (IH) induces overexpression of paraspeckle component 1 (PSPC1), a master modulator of transforming growth factor β (TGF-β) signaling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of IH-induced effect on PSPC1, and its consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma (CM) with or without OSA, and their relationship with tumor aggressiveness along with the in vitro effects of soluble PSPC1 and IH on melanoma cell aggressiveness mechanisms were assessed.In 292 CM patients, sleep studies and serum levels of PSPC1 and TGFβ were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and IH conditions.PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several CM clinical aggressiveness indicators. Both IH exposures and serum from OSA patients up-regulated TGFβ expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics.In CM patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with IH would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.