MiRNAs under condition of continuous and intermittent hypoxia: possible link with oncogenesis?

Abstract

<b>Introduction:</b> MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases including cancer [Croce CM et al. Cell. 2005 Jul 15;122(1):6-7]. MiRNAs expression can be influenced by various stimuli among which hypoxia; however, the effects of different types of hypoxia on miRNAs are still poorly studied. Lately, some hypoxia-regulated miRNAs (HRMs) have been identified [Kulshreshtha R et al. Mol Cell Biol. 2007 Mar;27(5):1859-67]. These HRMs are often activated in different types of cancers suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in intermittent hypoxia (IH) and in continuous hypoxia (CH) to better understand the possible relationship between hypoxia, miRNAs and cancer. <b>Methods:</b> We used RT-PCR to detect the miRNAs expression in colon-cancer cell lines in conditions of IH and CH. Expression of miRNAs was analyzed using two-way ANOVA test to compare the differential expression of miRNAs among IH, CH and normoxia. <b>Results:</b> The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210) were greater in CH versus IH, except for miR-23b and for miR-21. <b>Conclusions:</b> This study identified a series of miRNAs involved in the response to different types of hypoxia highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how IH and CH are able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis.