HIF-1α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia

Karagiota, Angeliki; Kourti, Maria; Simos, George; Mylonis, Ilias

doi:10.1007/s00018-018-2985-7

Cited by 42 publications

(38 citation statements)

References 59 publications

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“…Several interesting results from our study may promote further investigation into the functions and partners of miR-200s, push forward the clinical application of miR-200s and also provide us with more targets and strategies for therapy. Although not perfect, most of the findings from our results have been successfully confirmed by recent experimental literatures [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. To better confirm the predictive power of our approach and understand the mechanisms underlying the initiation and progression of CRC, more large-scale and standard investigations are worth conducting.…”

Section: Discussionsupporting

confidence: 71%

“…HIF-1, a transcription factor with important part in response to low oxygen concentrations, or hypoxia, play significant roles in normal tissue development and function and cancer progression [45]. Activation of the HIF-1 pathway has been considered as an attractive therapeutic target [46]. The Hippo signaling, made up of a core kinases module and transcriptional activation module, has recently emerged as an important biochemical signaling in regulating a variety of signaling processes such as organ development and maintenance of tissue homeostasis [47].…”

Section: Discussionmentioning

confidence: 99%

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Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Peng

Cheng

et al. 2020

Cancer Cell Int

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Background: Accumulating evidence has demonstrated that could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial. Methods:We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC. Results:Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01-1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein-protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC.Conclusions: Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Peng

Cheng

et al. 2020

Cancer Cell Int

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“…However, SAM treatment stabilizes USP1 at both mRNA and protein levels, suggesting that AMPK is regulated by SAM [ 188 ]. Interestingly, HIF-1α stabilizes the ERK1/2 target gene FOXM1 and mediates metabolic reprogramming regulated by AMPK under hypoxia in HCC [ 189 ]. Hypoxia decreases SAM levels in HCC cells, leading to reduced genomic DNA methylation levels [ 190 ].…”

Section: Influence Of Intracellular Metabolites On Hif-α Stability Thmentioning

confidence: 99%

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Mao

Wang

et al. 2020

J Exp Clin Cancer Res

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Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors.

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“…The structures included in HIF-1α and HIF-1β are basic-helix-loop-helix and PER-ARNT-SIM domain, which promote DNA binding and dimerization (9,23). Increasing evidence has indicated that HIF-1α, as the active subunit of HIF-1, is involved in inducing and maintaining the phenotype of various CSCs (12,24,25). The present review focused more on the association between HIF-1α and CSCs than of HIF-1.…”

Section: Structural Characteristics Of Hif-1mentioning

confidence: 98%

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

et al. 2020

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Cancer stem cells (CSCs) have been found to play a decisive role in cancer recurrence, metastasis, and chemo-, radio-and immuno-resistance. Understanding the mechanism of CSC self-renewal and proliferation may help overcome the limitations of clinical treatment. The microenvironment of tumor growth consists of a lack of oxygen, and hypoxia has been confirmed to induce cancer cell invasion, metastasis and epithelial-mesenchymal transition, and is usually associated with poor prognosis and low survival rates. Hypoxia inducible factor-1 (HIF-1) can be stably expressed under hypoxia and act as an important molecule to regulate the development of CSCs, but the specific mechanism remains unclear. The present review attempted to explain the role of HIF-1 in the generation and maintenance of CSCs from the perspective of epigenetics, metabolic reprogramming, tumor immunity, CSC markers, non-coding RNA and signaling pathways associated with HIF-1, in order to provide novel targets with HIF-1 as the core for clinical treatment, and extend the life of patients. Contents 1. Introduction 2. Structural characteristics of HIF-1 3. Role of epigenetic and post-translational modification of HIF-1 in CSCs 4. Role of HIF-1 in non-coding RNA associated with CSCs 5. Role of HIF-1 in CSC markers 6. Role of HIF-1 in tumor immunity of CSCs 7. Role of HIF-1 in metabolic reprogramming of CSCs 8. Role of HIF-1 in signaling pathways associated with CSCs 9. Potential targets for CSC therapy 10. Conclusions and perspectives

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HIF-1α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia

Cited by 42 publications

References 59 publications

Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

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