Hypoxia-inducible factor–1α–dependent induction of miR122 enhances hepatic ischemia tolerance

Ju, Cynthia; Wang, Meng; Tak, Eunyoung; Kim, Boyun; Emontzpohl, Christoph; Yang, Yang; Yuan, Xiaoyi; Kutay, Huban; Liang, Yafen; Hall, David R.; Dar, Wasim; Bynon, John S.; Carmeliet, Peter; Ghoshal, Kalpana; Eltzschig, Holger K.

doi:10.1172/jci140300

Cited by 43 publications

(31 citation statements)

References 57 publications

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“…Moreover, HIF-1α proved to be a miR-122 target in diet-induced steatohepatitis [ 20 ] and in a mouse model of HCC [ 21 ]. A very recent paper provided more insights about the interplay between miR-122 and hypoxia-induced pathways in a murine model of ischemia-reperfusion injury [ 22 ]. With this in mind, we evaluated the correlation between miR-21, miR-122, and HIF-1α in our group of patients treated with DEB-TACE, a treatment that induces liver ischemia and, in turn, over-expression of hypoxia-related genes.…”

Section: Discussionmentioning

confidence: 99%

“…miR-122, as recently demonstrated, targets HIF-1α in diet-induced steatohepatitis [ 20 ], with some data suggesting an interplay between the two molecules also in HCC [ 21 ]. Moreover, a very recent paper found a role of miR-122 in enhancing liver ischemia tolerance in a murine model of hepatic ischemia-reperfusion injury through its induction by HIF-1α [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

et al. 2021

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Background: MicroRNAs (miRNAs) have been proposed as biomarkers in hepatocellular carcinoma (HCC). We aim at evaluating miR-21 and miR-122 in HCC patients treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) as prognostic biomarkers and investigating their correlation with hypoxia inducible factor-1α (HIF-1α) serum levels. Methods: In this retrospective study, 12 healthy subjects, 28 cirrhotics, and 54 HCC patients (tested before and four weeks after DEB-TACE) were included. Whole blood miR-21 and miR-122 levels were measured by quantitative real time (qRT)-PCR, while serum HIF-1α was assessed by an enzyme-linked immunosorbent assay (ELISA) test. Results: The highest level of miR-21 was found in cirrhotics, while HCC patients had the highest level of miR-122 (which was even higher in “viral” HCC, p = 0.006). miR-21 ratio (after/before DEB-TACE) and miR-122 below their respective cut-offs identified patients with longer progression-free survival (p = 0.0002 and p = 0.02, respectively). The combined assessment of alpha-fetoprotein and miR-21 ratio, both independent prognostic predictors, identified early progressors among patients with complete or partial radiological response. miR-21 levels positively correlated with HIF-1α before (p = 0.045) and after DEB-TACE (p = 0.035). Conclusions: miR-21 ratio and miR-122 are useful prognostic markers after DEB-TACE. miR-21 correlates with HIF-1α and probably has a role in modulating angiogenesis in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

et al. 2021

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“…HIF-1α stability is partially mediated by the oxygen sensing prolyl hydroxylase domain 1 (PHD1), which under normoxic conditions tags HIF-1α for proteosomal degradation. Interestingly PHD1 function is repressed by miR122, a target gene of HIF-1α, which is almost exclusively expressed in hepatocytes[ 54 ]. By this mechanism, HIF-1α enhances HIF mediated cellular responses through PHD1 repression.…”

Section: What Are the Molecular Mediators Of Renal Injury Following Liver Ir Injury?mentioning

confidence: 99%

Literature review of the mechanisms of acute kidney injury secondary to acute liver injury

Platt¹,

Klootwijk²,

Salama³

et al. 2022

WJN

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People exposed to liver ischaemia reperfusion (IR) injury often develop acute kidney injury and the combination is associated with significant morbidity and mortality. Molecular mediators released by the liver in response to IR injury are the likely cause of acute kidney injury (AKI) in this setting, but the mediators have not yet been identified. Identifying the mechanism of injury will allow the identification of therapeutic targets which may modulate both liver IR injury and AKI following liver IR injury.

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“…Furthermore, miR-122 suppressed SIRT1 expression by binding to its 3′-UTR. HIF-1α induced miR-122, which targets prolyl hydroxylase domain 1 during hepatic ischemia and reperfusion injury [ 55 ]. Therefore, HIF-1α appears to exist upstream and downstream of miR-122, suggesting that a negative feedback loop may regulate the miR-122–HIF-1α axis.…”

Section: Major Mirnas In Hypoxic Signaling and Oxidative Stressmentioning

confidence: 99%

“…A phase I/II clinical trial for Huntington’s disease involving the delivery of pri-miR-451 via adeno-associated viral vectors has been reported [ 117 ]. Nanoparticle-based miRNA administration without viral vectors was recently developed for liver injury using nanoparticle-mediated miR122 overexpression via intravenous administration to a mouse ischemia/reperfusion injury model [ 55 ].…”

Section: Therapeutic Strategy Via Mirna–sirt2 Inhibitionmentioning

confidence: 99%

Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

Kaitsuka

Matsushita

2021

Cells

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The sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylase and ADP-ribosyl transferases plays key roles in aging, metabolism, stress response, and aging-related diseases. SIRT2 is a unique sirtuin that is expressed in the cytosol and is abundant in neuronal cells. Various microRNAs were recently reported to regulate SIRT2 expression via its 3′-untranslated region (UTR), and single nucleotide polymorphisms in the miRNA-binding sites of SIRT2 3′-UTR were identified in patients with neurodegenerative diseases. The present review highlights recent studies into SIRT2-mediated regulation of the stress response, posttranscriptional regulation of SIRT2 by microRNAs, and the implications of the SIRT2–miRNA axis in aging-related diseases.

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Hypoxia-inducible factor–1α–dependent induction of miR122 enhances hepatic ischemia tolerance

Cited by 43 publications

References 57 publications

Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

Literature review of the mechanisms of acute kidney injury secondary to acute liver injury

Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

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