Hypoxia causes changes in transcription of the genes that contribute to adaptation of the cells to low levels of oxygen. The main mechanism regulating cellular response to hypoxia is activation of hypoxia-inducible transcription factors (HIF), which include several isoforms and control expression of more than a thousand genes. HIF activity is regulated at various levels, including by small non-coding RNA molecules called microRNAs (miRNAs). miRNAs regulate cellular response to hypoxia by influencing activation of HIF, its degradation, and translation of HIF-dependent proteins. At the same time, HIFs also affect miRNAs biogenesis. Data on the relationship of a particular HIF isoform with miRNAs are contradictory, since studies have been performed using different cell lines, various types of experimental animals and clinical material, as well as at different oxygen concentrations and durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which has not been taken into account in the studies. This review analyzes the data on the effect of hypoxia on biogenesis and functioning of miRNAs, as well as on the effect of miRNAs on mRNAs of the genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.

One of the factors contributing to colorectal cancer (CRC) development is inflammation, which is mostly hypoxia-associated. This study aimed to characterize the morphological and molecular biological features of colon tumors in mice that were tolerant and susceptible to hypoxia based on colitis-associated CRC (CAC). Hypoxia tolerance was assessed through a gasping time evaluation in a decompression chamber. One month later, the animals were experimentally modeled for colitis-associated CRC by intraperitoneal azoxymethane administration and three dextran sulfate sodium consumption cycles. The incidence of tumor development in the distal colon in the susceptible to hypoxia mice was two times higher and all tumors (100%) were represented by adenocarcinomas, while in the tolerant mice, only 14% were adenocarcinomas and 86% were glandular intraepithelial neoplasia. The tumor area assessed on serially stepped sections was statistically significantly higher in the susceptible animals. The number of macrophages, CD3−CD19+, CD3+CD4+, and NK cells in tumors did not differ between animals; however, the number of CD3+CD8+ and vimentin+ cells was higher in the susceptible mice. Changes in the expression of genes regulating the response to hypoxia, inflammation, cell cycle, apoptosis, and epithelial barrier functioning in tumors and the peritumoral area depended on the initial mouse’s hypoxia tolerance, which should be taken into account for new CAC diagnostics and treatment approaches development.

Environmental pollution with microplastics (MPs) can have a negative impact on human health. Certain findings point to the relationship between MP and the development of inflammatory bowel diseases (IBD). We investigated the effect of MP consumption on the severity of chronic colitis in male C57BL/6 mice. The MP effect was modeled by drinking water consumption with a suspension of 5 μm PS particles at a concentration of 10 mg/L replacement for 12 weeks. Chronic colitis was induced by three seven-day cycles of 1% DSS consumption (starting from the 8th, 29th and 50th days of the experiment). We investigated inflammatory infiltration, the goblet cell volume fraction and the highly sulfated and neutral mucins content in them, the endocrine cell number, the ulcerative-inflammatory process prevalence, changes in the gene’s expression encoding tight junction proteins, glycocalyx components proapoptotic factor Bax and proliferation marker Mki67 in the colon, and TNFα, IL-1β, IL-6 and IL-10 cytokines content in the serum. In healthy mice, MP did not cause pathological changes in the colon; however, indirect data indicate an increase in colon permeability. In chronic colitis, MP leads to higher prevalence of all pathological changes in general, and ulcers in particular, in a greater number of crypt abscesses and enteroendocrine cells. MP consumption leads to a more severe chronic colitis course.

Recently, evidence indicating that microplastics (MPs) have a hazardous effect on human health is accumulating. The potential of MPs having a role in carcinogenesis was suggested. Therefore, the aim of this study was to evaluate MPs’ effect on colitis-associated colorectal cancer (CAC) development. The AOM/DSS-induced CAC model was reproduced in two groups of adult male C56BL/6 mice. One of these groups received MPs (5 μm polystyrene microbeads) with drinking water at a dose of 1.48 mg/kg/day throughout the experiment (12 weeks), and the other received water untreated with MPs. In the colons of mice that consumed MPs, there was a higher number of tumor nodules at the macroscopic level, a greater tumor prevalence on histological sections, more pronounced inflammatory infiltration, a higher goblet cell volume fraction, the content of highly sulfated mucins was found in them, and there were more tumors with increased enteroendocrine cell content. We did not find any MP effects on the claudins, mucins, proapoptotic factor Bax, or on the proliferation marker Mki67 gene expression in the medial colon, nor on the serum level of TNFα, IL-1β, IL-6, and IL-10 cytokines. Thus, MPs promote the CAC development in mice by exacerbating intestinal local inflammation and damaging the epithelial barrier, and MPs may represent a potential environmental cofactor contributing to CAC risk.

Humans and laboratory animals differ in their resistance to hypoxia, which affects the severity of inflammatory diseases and the rate of tumor progression. Therefore, it is necessary to search for methods for assessing the initial tolerance to oxygen deficiency and the risks of developing acute mountain sickness without direct hypoxia exposure on the organism. The literature describes assessments of oxygen deficiency tolerance assessing based on physiological and molecular parameters. The limitations of such methods include the need of expensive equipment use and highly qualified specialists involvement. In addition, in the studies presented in this review, the altitude, time and methods for achieving it, as well as the frequency of assessing the severity of acute mountain sickness varied significantly. It is necessary to continue research aimed at investigating biomarkers of tolerance to oxygen deficiency without direct hypoxia exposure using instrumental and laboratory diagnostics. This will allow developing new approaches for personalized prevention, diagnosis and treatment of inflammatory diseases and malignancies and, accordingly, improve the quality of life.