Exploring shared hypoxic pathways in cancer and obstructive sleep apnea: A critical review of extracellular vesicles-non-coding RNA signaling and biological plausibility

Hypoxia plays a central role in the pathophysiology of both cancer and obstructive sleep apnea (OSA), while through biologically distinct mechanisms. Chronic hypoxia (CH), typical of the tumor microenvironment (TME), drives angiogenesis, metabolic rewiring, and malignant progression, whereas intermittent hypoxia (IH), a hallmark of OSA, triggers fluctuating oxidative stress, sympathetic activation, and inflammatory signaling. In recent years, extracellular vesicles (EVs) and their non-coding RNA (ncRNA) cargo, particularly microRNAs (miRNAs) and circular RNAs (circRNAs), have emerged as critical mediators of hypoxia-induced intercellular communication. Hypoxia modifies EV biogenesis, release, and molecular cargo, enabling the transfer of adaptive or pathological signals to distant tissues. Growing but heterogeneous evidence suggests that IH may influence cancer biology through pathways partially convergent with tumor hypoxia; however, clinical findings remain insufficient to support a causal relationship between cancer and OSA. This review summarizes current knowledge on hypoxia biology, HIF-mediated signaling, and the regulatory effects of hypoxia on EV-ncRNA profiles. We also discuss the potential, yet not definitively established, role of OSA-related IH in modulating EV-ncRNA-dependent communication and highlight key gaps that must be addressed to clarify the translational relevance of these mechanisms.