MicroRNA-124 regulates glucocorticoid sensitivity by targeting phosphodiesterase 4B in diffuse large B cell lymphoma

Kim, Jin‐Young; Jeong, Dawoom; Nam, Jehyun; Aung, Thazin Nwe; Gim, Jeong‐An; Park, Keon Uk; Kim, Sang Woo

doi:10.1016/j.gene.2015.01.001

Cited by 37 publications

(23 citation statements)

References 42 publications

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“…It has been reported that miR-124 influenced apoptosis in regulation of AKT/mTOR/ MCL-1 survival pathway [18]. Here, we found that the mRNA (p < 0.05) and protein levels of MCL-1 was down-regulated by miR-124 mimic transfection, while was up-regulated by anti-miR-124 transfection ( Fig.…”

Section: Mcl-1 Is a Target Gene Of Mir-124supporting

confidence: 55%

Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

Yin

et al. 2018

Cell Physiol Biochem

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Background/Aims: HULC is a multifunctional lncRNA that has pro-angiogenic function in various cancers. The present study was designed to see the role of lncRNA HULC in normal endothelial cells angiogenesis. Methods: Cell viability, apoptosis, migration, tube formation and expression levels of angiogenesis-related proteins were respectively assessed in human microvascular endothelial HMEC-1 cells after lncRNA HULC was silenced by shRNA transfection. Cross-regulation between lncRNA HULC and miR-124, and between miR-124 and MCL-1 were detected by qRT-PCR, sequence analysis, and luciferase reporter assay. Results: Silence of lncRNA HULC significantly reduced viability, migration, tube formation and protein levels of VEGF, VEGFR2, CD144 and eNOS in HMEC-1 cells. Meanwhile, silence of lncRNA HULC induced apoptosis in HMEC-1 cells, as Bcl-2 was down-regulated, Bax was up-regulated, and caspase-3 and -9 were cleaved. miR-124 expression was negatively regulated by lncRNA HULC, and HULC worked as a molecular sponge for miR-124, in having miR-124 exhausted. Besides, MCL-1 was a target gene of miR-124. Rescue assay results showed that the effects of lncRNA HULC silence on HMEC-1 cells growth, migration and angiogenesis were abolished by miR-124 suppression. Similarly, the effects of miR-124 on HMEC-1 cells were abolished by MCL-1 overexpression. Furthermore, MCL-1 activated PI3K/AKT and JAK/STAT signaling pathways. Conclusion: These findings suggest a pro-angiogenic role of lncRNA HULC in endothelial cells. The pro-angiogenic actions of lncRNA HULC may be through sponging miR-124, preventing MCL-1 from degradation by miR-124.

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Section: Mcl-1 Is a Target Gene Of Mir-124supporting

confidence: 55%

Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

Yin

et al. 2018

Cell Physiol Biochem

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“…gov/pubmed/) using the query "predicted gene name" AND mTOR. We found that PDE4B was the only qualified gene that correlated with mTOR signaling and was targeted by miR-124-3p (33,45).…”

Section: Exosomal Mir-124-3p Inhibited Neuronal Inflammation By Supprmentioning

confidence: 87%

“…Analysis. The results suggest that PDE4B is the only qualified gene that correlates with mTOR signaling and is targeted by miR-124-3p (33,45). The family of PDE4 enzymes is an underexploited therapeutic target for neurologic diseases, as there are no amino acid sequence differences in the active site among the PDE4 subtypes.…”

Section: Discussionmentioning

confidence: 99%

Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowthviatheir transfer into neurons

et al. 2017

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Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro. The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs. We found that miR-124-3p promoted the anti-inflamed M2 polarization in microglia, and microglial exosomal miR-124-3p inhibited neuronal inflammation in scratch-injured neurons. Further, the mammalian target of rapamycin (mTOR) signaling was implicated as being involved in the regulation of miR-124-3p by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Using the mTOR activator MHY1485 we confirmed that the inhibitory effect of exosomal miR-124-3p on neuronal inflammation was exerted by suppressing the activity of mTOR signaling. PDE4B was predicted to be the target gene of miR-124-3p by pathway analysis. We proved that it was directly targeted by miR-124-3p with a luciferase reporter assay. Using a PDE4B overexpressed lentivirus transfection system, we suggested that miR-124-3p suppressed the activity of mTOR signaling mainly through inhibiting the expression of PDE4B. In addition, exosomal miR-124-3p promoted neurite outgrowth after scratch injury, characterized by an increase on the number of neurite branches and total neurite length, and a decreased expression on RhoA and neurodegenerative proteins [Ab-peptide and p-Tau]. It also improved the neurologic outcome and inhibited neuroinflammation in mice with rTBI. Taken together, increased miR-124-3p in microglial exosomes after TBI can inhibit neuronal inflammation and contribute to neurite outgrowth via their transfer into neurons. miR-124-3p exerted these effects by targeting PDE4B, thus inhibiting the activity of mTOR signaling. Therefore, miR-124-3p could be a promising therapeutic target for interventions of neuronal inflammation after TBI. miRNAs manipulated microglial exosomes may provide a novel therapy for TBI and other neurologic diseases.-Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., Lei, P. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J. 32, 512-528 (2018). www.fasebj.org

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“…Collectively, these findings suggest that miR-124-3p may be both a biomarker and therapeutic target for psychiatric disorders related to dysfunction of the HPA axis. It should be noted that several other putative targets of miR-124 have been identified (37), and miR-124 was reported to influence GR function indirectly via effects on phosphodiesterase 4B (38) or 11␤HSD1 (34).…”

Section: Regulation Of the Glucocorticoid Receptor By Mirnasmentioning

confidence: 99%

The role of microRNAs in glucocorticoid action

Jones

Kurowska‐Stolarska

et al. 2018

ESPE

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MicroRNA-124 regulates glucocorticoid sensitivity by targeting phosphodiesterase 4B in diffuse large B cell lymphoma

Cited by 37 publications

References 42 publications

Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowthviatheir transfer into neurons

The role of microRNAs in glucocorticoid action

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