Biosystem Analysis of the Hypoxia Inducible Domain Family Member 2A: Implications in Cancer Biology

Salazar, Celia; Yáñez, Osvaldo; Elorza, Álvaro A.; Cortés, Natalie; García‐Beltrán, Olimpo; Tiznado, William; Ruíz, Lina

doi:10.3390/genes11020206

Cited by 8 publications

(20 citation statements)

References 69 publications

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“…The expression dataset is freely available at Gene Expression Omnibus, accession number GSE145935. To confirm a robust response to hypoxia was induced, the dataset was interrogated to identify a comprehensive panel of published hypoxia-inducible genes [ 22 , 23 , 24 ], as shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of Human Astrocytes In Vitro Reveals Hypoxia-Induced Mitochondrial Dysfunction, Modulation of Metabolism, and Dysregulation of the Immune Response

Allen

Seehra

Heath

et al. 2020

IJMS

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Hypoxia is a feature of neurodegenerative diseases, and can both directly and indirectly impact on neuronal function through modulation of glial function. Astrocytes play a key role in regulating homeostasis within the central nervous system, and mediate hypoxia-induced changes in response to reduced oxygen availability. The current study performed a detailed characterization of hypoxia-induced changes in the transcriptomic profile of astrocytes in vitro. Human astrocytes were cultured under normoxic (5% CO2, 95% air) or hypoxic conditions (1% O2, 5% CO2, 94% N2) for 24 h, and the gene expression profile assessed by microarray analysis. In response to hypoxia 4904 genes were significantly differentially expressed (1306 upregulated and 3598 downregulated, FC ≥ 2 and p ≤ 0.05). Analysis of the significant differentially expressed transcripts identified an increase in immune response pathways, and dysregulation of signalling pathways, including HIF-1 (p = 0.002), and metabolism, including glycolysis (p = 0.006). To assess whether the hypoxia-induced metabolic gene changes observed affected metabolism at a functional level, both the glycolytic and mitochondrial flux were measured using an XF bioanalyser. In support of the transcriptomic data, under physiological conditions hypoxia significantly reduced mitochondrial respiratory flux (p = 0.0001) but increased basal glycolytic flux (p = 0.0313). However, when metabolically stressed, hypoxia reduced mitochondrial spare respiratory capacity (p = 0.0485) and both glycolytic capacity (p = 0.0001) and glycolytic reserve (p < 0.0001). In summary, the current findings detail hypoxia-induced changes in the astrocyte transcriptome in vitro, identifying potential targets for modifying the astrocyte response to reduced oxygen availability in pathological conditions associated with ischaemia/hypoxia, including manipulation of mitochondrial function, metabolism, and the immune response.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of Human Astrocytes In Vitro Reveals Hypoxia-Induced Mitochondrial Dysfunction, Modulation of Metabolism, and Dysregulation of the Immune Response

Allen

Seehra

Heath

et al. 2020

IJMS

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“…In addition, it increased in the liver and spleen tissue (increased hypoxia) due to the rapid proliferation of tissue, while in healthy mice, the expression of this gene in the bone marrow and spleen increased but it decreased in the liver. Finally, they found that HIGD2A gene expression increased in DLBCL cells and decreased in nodal marginal lymphoma (NMZL) [ 82 ].…”

Section: Quercetin and Lymphomasmentioning

confidence: 99%

Quercetin as a Novel Therapeutic Approach for Lymphoma

Soofiyani

Hosseini

Forouhandeh

et al. 2021

Oxidative Medicine and Cellular Longevity

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Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.

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“…Moreover, the silencing of HIGD2A alters the viability of DLD1 colon adenocarcinoma cells, indicating that silencing HIGD2A induces death in cancer cells, suggesting a role for HIG2A in cell cycle regulation and a potential target in cancer therapy [ 16 ]. Remarkably, DNA methylation and mRNA expression in the HIGD2A gene showed significant alterations in various cancers [ 17 ]. The correlation between high HIGD2A expression and poor patient survival is significant for hepatocellular carcinoma, cutaneous melanoma, endometrial carcinoma, and uveal melanoma [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, DNA methylation and mRNA expression in the HIGD2A gene showed significant alterations in various cancers [ 17 ]. The correlation between high HIGD2A expression and poor patient survival is significant for hepatocellular carcinoma, cutaneous melanoma, endometrial carcinoma, and uveal melanoma [ 17 ]. All the above-presented studies suggest a role for HIG2A in mitochondrial physiology and cancer biology.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Distribution of HIG2A between the Mitochondria and the Nucleus in Response to Hypoxia and Oxidative Stress

Salazar

Barros

Elorza

et al. 2021

IJMS

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Mitochondrial respiratory supercomplex formation requires HIG2A protein, which also has been associated with cell proliferation and cell survival under hypoxia. HIG2A protein localizes in mitochondria and nucleus. DNA methylation and mRNA expression of the HIGD2A gene show significant alterations in several cancers, suggesting a role for HIG2A in cancer biology. The present work aims to understand the dynamics of the HIG2A subcellular localization under cellular stress. We found that HIG2A protein levels increase under oxidative stress. H2O2 shifts HIG2A localization to the mitochondria, while rotenone shifts it to the nucleus. HIG2A protein colocalized at a higher level in the nucleus concerning the mitochondrial network under normoxia and hypoxia (2% O2). Hypoxia (2% O2) significantly increases HIG2A nuclear colocalization in C2C12 cells. In HEK293 cells, chemical hypoxia with CoCl2 (>1% O2) and FCCP mitochondrial uncoupling, the HIG2A protein decreased its nuclear localization and shifted to the mitochondria. This suggests that the HIG2A distribution pattern between the mitochondria and the nucleus depends on stress and cell type. HIG2A protein expression levels increase under cellular stresses such as hypoxia and oxidative stress. Its dynamic distribution between mitochondria and the nucleus in response to stress factors suggests a new communication system between the mitochondria and the nucleus.

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Biosystem Analysis of the Hypoxia Inducible Domain Family Member 2A: Implications in Cancer Biology

Cited by 8 publications

References 69 publications

Transcriptomic Analysis of Human Astrocytes In Vitro Reveals Hypoxia-Induced Mitochondrial Dysfunction, Modulation of Metabolism, and Dysregulation of the Immune Response

Transcriptomic Analysis of Human Astrocytes In Vitro Reveals Hypoxia-Induced Mitochondrial Dysfunction, Modulation of Metabolism, and Dysregulation of the Immune Response

Quercetin as a Novel Therapeutic Approach for Lymphoma

Dynamic Distribution of HIG2A between the Mitochondria and the Nucleus in Response to Hypoxia and Oxidative Stress

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