Glucocorticoid‐induced microRNA‐511 protects against
            <scp>TNF</scp>
            by down‐regulating
            <scp>TNFR</scp>
            1

Puimège, Leen; Hauwermeiren, Filip Van; Steeland, Sophie; Ryckeghem, Sara Van; Vandewalle, Jolien; Lodens, Sofie; Dejager, Lien; Vandevyver, Sofie; Staelens, Jan; Timmermans, Steven; Vandenbroucke, Roosmarijn E.; Libert, Claude

doi:10.15252/emmm.201405010

Cited by 39 publications

(33 citation statements)

References 47 publications

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“…It has been previously shown that peripheral miR-511 expression in the spleen and liver can be up-regulated by glucocorticoids (25). The current study confirmed this result in the brain, demonstrating that chronic corticosterone increased miR-511 expression.…”

Section: Discussionsupporting

confidence: 88%

“…This decrease in miR-511 levels may partially mediate the age-dependent elevations in FKBP5 expression. Interestingly, peripheral miR-511 expression in the spleen and liver can be up-regulated by glucocorticoids similar to FKBP5 (25). Therefore, we investigated whether miR-511 expression in the brain was affected by chronic glucocorticoid treatment in WT mice.…”

Section: Resultsmentioning

confidence: 99%

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MicroRNA-511 Binds to FKBP5 mRNA, Which Encodes a Chaperone Protein, and Regulates Neuronal Differentiation

Zheng

Sabbagh

Blair

et al. 2016

Journal of Biological Chemistry

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Single nucleotide polymorphisms in the FKBP5 gene increase the expression of the FKBP51 protein and have been associated with increased risk for neuropsychiatric disorders such as major depression and post-traumatic stress disorder. Moreover, levels of FKBP51 are increased with aging and in Alzheimer disease, potentially contributing to disease pathogenesis. However, aside from its glucocorticoid responsiveness, little is known about what regulates FKBP5. In recent years, non-coding RNAs, and in particular microRNAs, have been shown to modulate disease-related genes and processes. The current study sought to investigate which miRNAs could target and functionally regulate FKBP5. Following in silico data mining and initial target expression validation, miR-511 was found to suppress FKBP5 mRNA and protein levels. Using luciferase p-miR-Report constructs and RNA pulldown assays, we confirmed that miR-511 bound directly to the 3-UTR of FKBP5, validating the predicted gene-microRNA interaction. miR-511 suppressed glucocorticoidinduced up-regulation of FKBP51 in cells and primary neurons, demonstrating functional, disease-relevant control of the protein. Consistent with a regulator of FKBP5, miR-511 expression in the mouse brain decreased with age but increased following chronic glucocorticoid treatment. Analysis of the predicted target genes of miR-511 revealed that neurogenesis, neuronal development, and neuronal differentiation were likely controlled by these genes. Accordingly, miR-511 increased neuronal differentiation in cells and enhanced neuronal development in primary neurons. Collectively, these findings show that miR-511 is a functional regulator of FKBP5 and can contribute to neuronal differentiation. FKBP51 (FK506 binding protein 51 kDa) is dysregulated in several diseases, but there is a paucity of data regarding its functional regulation. FKBP51 is an Hsp90 co-chaperone that helps regulate the function of specific Hsp90 clients, such as the glucocorticoid receptor (GR) 3 and the microtubule-associated protein Tau. FKBP51 inhibits GR function, leading to delayed hypothalamic-pituitary-adrenal axis feedback and elevated circulating glucocorticoid levels (1-3), a phenomenon observed in major depression (4). In fact, single nucleotide polymorphisms in the FKBP5 gene have been associated with increased risk for depression, as well as other neuropsychiatric disorders including post-traumatic stress disorder (PTSD) (5-7). Mice with a targeted deletion of Fkbp5 display resilience to stress and accelerated hypothalamic-pituitary-adrenal axis reactivity (8, 9). FKBP51 expression is also increased in Alzheimer disease (AD), which is characterized by accumulation of misfolded Tau (10). FKBP51 has been shown to accelerate Tau oligomerization and neurotoxicity in vitro and in vivo, suggesting that it may be contributing to the pathogenesis of AD (11). Therefore, reducing FKBP51 expression is of significant interest in both depression and AD; however, little is known about what genetically regulates FKBP5, aside from...

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

MicroRNA-511 Binds to FKBP5 mRNA, Which Encodes a Chaperone Protein, and Regulates Neuronal Differentiation

Zheng

Sabbagh

Blair

et al. 2016

Journal of Biological Chemistry

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“…In SPRET/Ei mice, glucocorticoid induced miR-511 upregulation, inhibiting the TNF receptor TNFR1 and, hence, reducing their sensitivity to TNF-α [135]. Similarly, administration of dexamethasone in a LPS-induced murine sepsis model downregulated the expression of miR-155 in the liver and alleviated proinflammatory cytokine production [116, 138].…”

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

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BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

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“…Induction of TNF-α by HCV is dependent on Toll-like receptor (TLR) 7 and TLR8. Form recognition receptors seen in many cell types that participate in the innate immune response associated with viral infections and viral antigens are called TLRs (15). TNF binds to two receptors, TNFR1 and TNFR2; the first is structurally expressed in most cells, the second is inducible and has a more limited expression pattern (16).…”

Section: Introductionmentioning

confidence: 99%

TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

Günal¹,

Yalçin²,

Çelik³

et al. 2017

vhd

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ÖZObjective: We aimed to review the influence of host genetic factors on the clinical course, treatment response as well as fibrosis progression in patients with viral hepatitis C genotype 1. Materials and Methods: Ninety-five patients with chronic hepatitis C virus (HCV) infection and 97 controls were enrolled. The patients received pegylated interferon (Peg-IFN)+ribavirin therapy for 48 weeks and were followed up for the next 48 weeks. Aspartat aminotransferase/platelet ratio (APRI) was used to detect liver fibrosis DNA specimens were extracted from the peripheral blood mononuclear cells and the tumor necrosis factor-alpha (TNF-α) 308 rs3091256 was genotyped by the polymerase chain reactionrestriction fragment length polymorphism method. Results: All patients included in the study were infected with HCV genotype 1. of the 95 HCV-positive patients, spontaneous viral clearence was observed in 25.5%, rapid viral response in 44.2%, early viral response in 91.8%, and sustained viral response was found in 73.3% of patients. The allele and genotype were not significant between patients and controls. There was no significant difference in virologic response as well. However, TNF-α-308 single nucleotide polymorphisms (SNP) rs3091256 GG genotype was strongly associated with fibrosis and alanine aminotransferase (ALT) levels (p=0.006 and p=0.017, respectively). Conclusion: TNF-α-308 polymorphisms may reveal different results among countries. Patients having SNP rs3091256 GG are prone to have higher ALT levels and fibrosis score but have better treatment outcome.

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Glucocorticoid‐induced microRNA‐511 protects against TNF by down‐regulating TNFR 1

Cited by 39 publications

References 47 publications

MicroRNA-511 Binds to FKBP5 mRNA, Which Encodes a Chaperone Protein, and Regulates Neuronal Differentiation

MicroRNA-511 Binds to FKBP5 mRNA, Which Encodes a Chaperone Protein, and Regulates Neuronal Differentiation

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

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