Background: Obstructive sleep apnea (OSA) is a sleep breathing disorder associated with an increased cancer risk, but the mechanisms underlying this link remain poorly understood. Several miRNAs are involved in cancer development and progression. Their expression can be influenced by hypoxia. The main aim of this experimental study was to evaluate changes in miRNAs expression in controls or patients affected by OSA and/or cancer and in colorectal cancer cells exposed to intermittent hypoxia (IH), and to evaluate their impact on tumor progression in vitro.

Methods: We detected miRNAs by qRT-PCR in patients? sera and in CaCo2 cells exposed to 2 to 32h of IH with or without acriflavine, a HIF-1 inhibitor. MTT and transwell invasion test were applied to investigate the proliferation and migration of CaCo2 exposed to IH and treated with miRNA inhibitors or acriflavine. HIF-1? activity was evaluated in CaCo2 cells after IH.

Results: The levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145 increased in OSA but not ONCO-OSA patients. MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. IH stimulated cell proliferation and migration, that were reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1? gene expression. Conversely, acriflavine reduced the expression of these miRNAs.

Conclusions: We identified a series of miRNAs, induced by the hypoxic environment, in malignancies associated with OSA. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1.