Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes

Tirpe, Alexandru; Gulei, Diana; Ciortea, Stefana Maria; Crivii, Carmen; Berindan‐Neagoe, Ioana

doi:10.3390/ijms20246140

Cited by 258 publications

(201 citation statements)

References 137 publications

(144 reference statements)

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“…Chronic hypoxia activates signaling pathways that cause angiogenesis [112]-a proliferation of blood vessels that supply the growing tumor with oxygen. Nevertheless, such vessels exhibit certain structural abnormalities [113] which results in their leakiness [114], and lack of a conventional hierarchy [114,115].…”

Section: Cycling Hypoxiamentioning

confidence: 99%

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Korbecki

Kojder

Barczak

et al. 2020

IJMS

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Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and tumor-associated macrophages (TAM) to a tumor niche.

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Section: Cycling Hypoxiamentioning

confidence: 99%

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Korbecki

Kojder

Barczak

et al. 2020

IJMS

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“…HIF-1α, recognized as oxygen-labile subunit of HIF-1, contains the transactivation domains responsible for HIF-1α transcriptional activity [21,22]. Despite the fact that HIF-1α is merely highly expressed during hypoxic condition, it is also detectable in normoxic condition.…”

Section: Discussionmentioning

confidence: 99%

MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC

Yang

Zheng

Tan

et al. 2020

Preprint

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Background Non-small cell lung cancer (NSCLC), is the most common malignancy worldwide. MiR-199a-5p has been reported to play important roles in multiple tumors, inclusive of NSCLC. Whereas, little is definitively known pertaining to its explicit mechanism of action in NSCLC. Methods Expression of miR-199a-5p and HIF-1α mRNA were quantified employing qRT-PCR. H1299 and A549 cells were transiently transfected with miR-199a-5p mimics or inhibitors. Then CCK-8 assays, flow cytometry analysis, Transwell assay were implemented for detecting cell proliferation, cell cycle, apoptosis, migration and invasion of NSCLC cells, respectively. HIF-1α, STAT3 and p-STAT3 expression were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed for monitoring interaction between miR-199a-5p, HIF-1α and STAT3. Xenograft models were established with nude mice for further analyzing Bevacizumab resistance of NSCLC. Results MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p constrained proliferation, migration, invasion but induced apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. Further study confirmed a positive feed-back loop between miR-199a-5p, HIF-1α and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted effects of miR-199a-5p. Further study substantiated that feed-back loop might be in association with the Bevacizumab resistance of NSCLC cells . Conclusion MiR-199a-5p constrained the progression and Bevacizumab resistance of NSCLC by suppressing HIF-1α and STAT3, while HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feed-back loop to promote the sustaining progression of NSCLC.

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“…291 HIF-1α is a TF, which can be degraded by prolyl hydroxylases, such as PHD2, under normoxic conditions. 292 Notably, lack of oxygen can inactivate PHD, leading to the accumulation and subsequent activation of HIF-1α. Activated HIF-1α can directly bind to the hypoxia-responsive element of the promoter of several EMT-associated genes, such as TWIST1 and TGF-β, to stimulate the induction of EMT.…”

Section: Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 99%

Emerging role of tumor cell plasticity in modifying therapeutic response

Qin

Jiang

Lü

et al. 2020

Sig Transduct Target Ther

141

122

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Resistance to cancer therapy is a major barrier to cancer management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that will be discussed here. Such non-mutational processes are largely driven by tumor cell plasticity, which renders tumor cells insusceptible to the drug-targeted pathway, thereby facilitating the tumor cell survival and growth. The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition, acquisition properties of cancer stem cells, and trans-differentiation potential during drug exposure. From observations in various cancers, this concept provides an opportunity for investigating the nature of anticancer drug resistance. Over the years, our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased. This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs, which are likely to improve patient outcomes in clinical practice.

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Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes

Cited by 258 publications

References 137 publications

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC

Emerging role of tumor cell plasticity in modifying therapeutic response

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