Hypoxia-Induced circRNAs in Human Diseases: From Mechanisms to Potential Applications

Huang, Qi; Yang, Juan; Goh, Robby Miguel; You, Ming; Wang, Lingzhi; Ma, Zhaowu

doi:10.3390/cells11091381

Cited by 5 publications

(2 citation statements)

References 110 publications

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“…Thus, several adaptive cellular responses and biological changes are initiated when cancer cells sense a drop in oxygen levels, causing them to swiftly adapt to the hypoxic environment and accelerate cancer progression ( 182 ). Recent studies have revealed that circRNAs play crucial roles in developing hypoxic microenvironments and exhibit variable expression in response to hypoxia ( 183 , 184 ). According to previous studies, miR-497-5p is targeted by PRKAA1 and contributes to ESCC cell proliferation and motility control by being minimally expressed in ESCC ( 185 ).…”

Section: Circrnas As a Novel Regulator Of Tumor Microenvironment In Esccmentioning

confidence: 99%

Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment

Yao

Cai

et al. 2023

Front. Oncol.

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Esophageal squamous cell carcinoma (ESCC) is the most prevalent histological esophageal cancer characterized by advanced diagnosis, metastasis, resistance to treatment, and frequent recurrence. In recent years, numerous human disorders such as ESCC, have been linked to abnormal expression of circular RNAs (circRNAs), suggesting that they are fundamental to the intricate system of gene regulation that governs ESCC formation. The tumor microenvironment (TME), referring to the area surrounding the tumor cells, is composed of multiple components, including stromal cells, immune cells, the vascular system, extracellular matrix (ECM), and numerous signaling molecules. In this review, we briefly described the biological purposes and mechanisms of aberrant circRNA expression in the TME of ESCC, including the immune microenvironment, angiogenesis, epithelial-to-mesenchymal transition, hypoxia, metabolism, and radiotherapy resistance. As in-depth research into the processes of circRNAs in the TME of ESCC continues, circRNAs are promising therapeutic targets or delivery systems for cancer therapy and diagnostic and prognostic indicators for ESCC.

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Section: Circrnas As a Novel Regulator Of Tumor Microenvironment In Esccmentioning

confidence: 99%

Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment

Yao

Cai

et al. 2023

Front. Oncol.

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“…Hypoxia refers to a condition in which there is an insufficient supply of oxygen to tissues and cells in the body (Lee et al, 2019). It can be caused by various factors, such as high altitude, lung disease, or reduced blood flow (Huang et al, 2022). When cells do not get enough oxygen, their normal function is compromised, leading to potential health problems.…”

Section: Introductionmentioning

confidence: 99%

Adaptive Effects of Intermittent Hypoxia Training on Oxygen-Dependent Processes as a Potential Therapeutic Strategy Tool

Kurhaluk

2024

Cell Physiol Biochem

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Background/Aims: Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session. Methods: We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation. Results: The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment. Conclusion: Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole.

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Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets

Nisar,

Khan,

et al. 2024

MedComm

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Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age‐related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia‐targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia‐induced pathways to enhance healthy aging and reduce the burden of age‐related diseases.

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Hypoxia-Induced circRNAs in Human Diseases: From Mechanisms to Potential Applications

Cited by 5 publications

References 110 publications

Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment

Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment

Adaptive Effects of Intermittent Hypoxia Training on Oxygen-Dependent Processes as a Potential Therapeutic Strategy Tool

Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets

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