Argonaute‐2 Promotes miR‐18a Entry in Human Brain Endothelial Cells

Santos, Tiago; Amar, Arun Paul; Gong, Alex; Chen, Thomas C.; Tahara, Stanley M.; Giannotta, Steven L.; Hofman, Florence M.

doi:10.1161/jaha.114.000968

Cited by 27 publications

(33 citation statements)

References 25 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…D: ChIP PCR was conducted with the resulting precipitated DNA. miR-18a was expressed in AVM-derived brain ECs and that Ago-2 facilitated miR-18a entry into brain ECs and affected vascular formation in patients of cerebral arteriovenous malformation (Dews et al, 2006;Ferreira et al, 2014). The overexpression of miR-18a significantly inhibited three-dimensional spheroid sprouting in vitro (Doebele et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…miR-18a, as an important member of the miR-17-92 cluster, has certain impacts on angiogenesis, tumor invasion, and metastasis in gastric cancer and hepatocellular carcinoma Wu et al, 2013). Ferreira et al (2014) showed that miR-18a was expressed in cerebral vascular endothelium and that Ago-2 could promote miR-18a entry in brain endothelial cells (ECs) and angiogenesis in cerebral arteriovenous malformation (Dews et al, 2006). However, whether miR-18a was involved in regulating the function of glioma vascular endothelial cells (GECs) as well as permeability of the blood-tumor barrier (BTB) still remained unclear.…”

Section: Keymentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of miR‐18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood–tumor barrier via Krüppel‐like factor 4‐mediated downregulation of zonula occluden‐1, claudin‐5, and occludin

Zhao

Wang

et al. 2015

J of Neuroscience Research

View full text Add to dashboard Cite

miR-18a represses angiogenesis and tumor evasion by weakening vascular endothelial growth factor and transforming growth factor-β signaling to prolong the survival of glioma patients, although it is thought to be an oncogene. This study investigates the potential effects of miR-18a on the permeability of the blood-tumor barrier (BTB) and its possible molecular mechanisms. An in vitro BTB model was successfully established. The endogenous expression of miR-18a in glioma vascular endothelial cells (GECs) was significantly lower than that in normal vascular ECs, and the overexpression of miR-18a significantly increased the permeability of the BTB as well as downregulating the mRNA and protein expressions of tight junction-related proteins zonula occluden-1 (ZO-1), claudin-5, and occludin in GECs. Dual luciferase reporter assays revealed that miR-18a bound to the 3'-untranslated region (3'UTR) of myocyte enhancer factor 2D (MEF2D). The overexpression of both miR-18a and MEF2D with the 3'UTR significantly weakened the effect caused by miR-18a of decreasing the mRNA and protein expressions of ZO-1, claudin-5 and occludin and of increasing the permeability of the BTB. Chromatin immunoprecipitation showed that MEF2D could directly bind to KLF4 promoter. This study shows that miR-18a targets and negatively regulates MEF2D, which further regulates tight junction-related proteins ZO-1, claudin-5, and occludin through transactivation of KLF4 and, finally, changes the permeability of the BTB. MiR-18a should garner growing attention because it might serve as a potential target in opening the BTB and providing a new strategy for the treatment of gliomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Keymentioning

confidence: 99%

Overexpression of miR‐18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood–tumor barrier via Krüppel‐like factor 4‐mediated downregulation of zonula occluden‐1, claudin‐5, and occludin

Zhao

Wang

et al. 2015

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…Non-vesicle associated miRNAs are also transferred to recipient cells and affect gene expression [12,13,47]. Effects of HDL/miRNA uptake by recipient cells have been noted [12,13], and Ago2-associated miR-18a from diseased brain endothelial H. Iftikhar and G. E. Carney Prospects & Overviews .... cells is internalized by non-diseased brain endothelial cells but not by other cell types tested [47].…”

Section: Is There Evidence For Functionality Of Uptaken Mirnas In Recmentioning

confidence: 99%

“…The strategies that researchers used to deliver miRNAs in vivo varied and included injections of vesicles, miRNAs or antagomirs into the bloodstream or specific tissues; in other studies cells expressing miRNAs were injected or vesicles were implanted directly into tissues [32,38,47,61,[74][75][76]. In many cases it is not clear from these experiments how the amount of exogenously supplied miRNA compares to the amount present in normal or diseased animals.…”

Section: Mirnas Are Taken Up and Alter Recipient Cell Gene Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Evidence and potential in vivo functions for biofluid miRNAs: From expression profiling to functional testing

Iftikhar

Carney

2016

BioEssays

View full text Add to dashboard Cite

A controversial hypothesis in RNA biology is that extracellular microRNAs (miRNAs), including those in biofluids, have non-cell-autonomous activities. Several studies have characterized biofluid miRNA profiles in healthy or diseased individuals but generally have failed to identify distinct disease signatures. It remains unclear whether alterations in fluid miRNA levels are simply indicators of physiological change or whether miRNAs are taken up by new cells at concentrations sufficient to affect gene expression. There are limitations to biofluid miRNA studies performed to date: methodology for isolating and quantifying biofluid miRNAs is not standardized across studies; mechanistic details of miRNA release and uptake are incomplete; and efforts to assess non-cell-autonomous effects of extracellular miRNAs have employed predominantly in vitro strategies. We describe controversies and questions that need to be addressed to test possible in vivo roles of extracellular miRNAs and propose model organisms with rich genetic toolkits for carrying out in vivo functional analyses.

show abstract

LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF‐1α/VEGF signaling in ischemic stroke

Zhang

Luo²,

Chen³

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Studies have shown that long noncoding ribonucleic acids (lncRNAs) play critical roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene 1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have not yet been reported. In the present study, we found that SNHG1 expression was remarkably increased both in isolated cerebral micro-vessels of a middle cerebral artery occlusion (MCAO) mice model, and in oxygen-glucose deprivation (OGD)-cultured mice brain micro-vascular endothelial cells (BMECs), meanwhile, the SNHG1 level was negatively correlated with miR-18a in MCAO mice. Mechanistically, SNHG1 inhibition presents larger brain infarct size and worsens neurological scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also significantly increased caspase-3 activity and cell apoptosis in OGD-cultured BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA (ceRNA) for miR-18a, thereby regulating the de-repression of its endogenous target HIF-1α and promoting BMEC survival through HIF-1α/VEGF signaling. This study found a neuroprotective effect of SNHG1 mediated by HIF-1α/VEGF signaling through acting as a ceRNA for miR-18a. These findings reveal a novel function of SNHG1, which contributes to an extensive understanding of ischemic stroke and provides novel therapeutic options for this disease.

show abstract

Argonaute‐2 Promotes miR‐18a Entry in Human Brain Endothelial Cells

Cited by 27 publications

References 25 publications

Overexpression of miR‐18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood–tumor barrier via Krüppel‐like factor 4‐mediated downregulation of zonula occluden‐1, claudin‐5, and occludin

Overexpression of miR‐18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood–tumor barrier via Krüppel‐like factor 4‐mediated downregulation of zonula occluden‐1, claudin‐5, and occludin

Evidence and potential in vivo functions for biofluid miRNAs: From expression profiling to functional testing

LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF‐1α/VEGF signaling in ischemic stroke

Contact Info

Product

Resources

About