Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis

Abstract

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. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. 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 moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis.

The Genes–Stemness–Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints

“…Other forms of ncRNAs include long non-coding RNAs (lncRNA), PIWI-interacting RNAs (piRNA), small interfering RNAs (siRNA), and microRNAs (miRNA) [ 137 , 138 ]. It is well known that the hypoxic microenvironment in MPM interferes with a range of miRNAs and that some miRNAs target HIF1α [ 139 , 140 , 141 , 142 ]. With respect to MPM, published data point out that let-7c-5p and miR-151-5p can be considered “hypoxamiRs” involved in tumor initiation and EMT maintenance, altered metabolism, chemoresistance, and poor prognosis [ 78 ].…”

The Burden of Respiratory Alterations during Sleep on Comorbidities in Obstructive Sleep Apnoea (OSA)

“…NH appears to involve a hypoxia-inducible factor (HIF), a regulator of oxygen metabolism, with activation of various pathophysiological pathways that cause the risk of developing chronic diseases such as diabetes, insulin resistance or cardiovascular diseases [ 12 , 13 , 14 ].…”

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“…In general, the alterations of gas exchanges during sleep cause an increased risk of a large number of diseases [ 5 ]. Several studies have demonstrated a directly proportional relationship between the number of cardiovascular risk factors, such as the development of arrhythmias, and OSA severity [ 6 , 7 , 8 ].…”