Intermittent Hypoxia Mediates Cancer Development and Progression Through HIF-1 and miRNA Regulation

• Giorgia Moriondo ^[1] ; Piera Soccio ^[1] ; Mélanie Minoves ^[2] ; Giulia Scioscia ^[1] ; Pasquale Tondo ^[1] ; Maria Pia Foschino Barbaro ^[1] ; Jean-Louis Pépin ^[2] ; Anne Briançon-Marjollet ^[2] ; Donato Lacedonia ^[1]
  1. [1] University of Foggia

     University of Foggia

     Foggia, Italia

     
  2. [2] University Grenoble Alpes, INSERM U1300, CHU Grenoble Alpes, HP2 Laboratory, Grenoble, France
• Localización: Archivos de bronconeumología: Organo oficial de la Sociedad Española de Neumología y Cirugía Torácica SEPAR y la Asociación Latinoamericana de Tórax ( ALAT ), ISSN 0300-2896, Vol. 59, Nº. 10 (October), 2023, págs. 629-637
• Idioma: inglés
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• Resumen

  • Introduction There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs are involved in cancer development and progression with expression being influenced by hypoxia.

    The aims of this work were (i) to compare miRNAs expression in controls versus patients affected by OSA without or with cancer (ONCO-OSA) and (ii) in colorectal cancer cells exposed to intermittent hypoxia (IH), to evaluate miRNAs impact on tumor progression in vitro.

    Methods We detected miRNAs by qRT-PCR in patients’ sera and in CaCo2 cells exposed to 2–32 h of IH with or without acriflavine (ACF), a HIF-1 inhibitor. Viability 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-1α 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. This effect was reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1α gene expression. Conversely, acriflavine reduced the expression of these miRNAs.

    Conclusions We identified a signature of miRNAs, induced by the IH environment. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1.