MicroRNA-182-5p attenuates cerebral ischemia-reperfusion injury by targeting Toll-like receptor 4

Ji, Wang; Xu, Zhimin; Chen, Xiufen; Li, Yan; Chen, Chen; Wang, Chongwu; Zhu, Jianwei; Wang, Zhaotao; Chen, Wenjin; Xiao, Zongyu; Xu, Ran

doi:10.1016/j.bbrc.2018.09.165

Cited by 68 publications

(37 citation statements)

References 23 publications

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“…6A-C), suggesting that P. aeruginosa-induced miR-183/96/182 upregulation in Mf is mediated by LPS/TLR4 pathway and that miR-183/ 96/182 may mediate P. aeruginosa-and LPS-induced immune/ inflammatory response of the Mf. Recently, several groups reported that TLR4 is a direct target of miR-182 by target luciferase reporter assays (44)(45)(46)(47)(48)(49). Consistent with these reports, our target prediction analysis using the TargetScan algorithm (TargetScan.org) showed multiple putative target sites of miR-182, miR-96, and miR-183 in the 39 UTR of mouse TLR4 transcript (Fig.…”

Section: Resultssupporting

confidence: 87%

The miR-183/96/182 Cluster Regulates the Functions of Corneal Resident Macrophages

et al. 2020

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Tissue-resident macrophages (ResMf) play important roles in the normal development and physiological functions as well as tissue repair and immune/inflammatory response to both internal and external insults. In cornea, ResMf are critical to the homeostasis and maintenance, wound healing, ocular immune privilege, and immune/inflammatory response to injury and microbial infection. However, the roles of microRNAs in corneal ResMf are utterly unknown. Previously, we demonstrated that the conserved miR-183/ 96/182 cluster (miR-183/96/182) plays important roles in sensory neurons and subgroups of both innate and adaptive immune cells and modulates corneal response to bacterial infection. In this study, we provide direct evidence that the mouse corneal ResMf constitutively produce both IL-17f and IL-10. This function is regulated by miR-183/96/182 through targeting Runx1 and Maf, key transcriptional regulators for IL-17f and IL-10 expression, respectively. In addition, we show that miR-183/96/182 has a negative feedback regulation on the TLR4 pathway in mouse corneal ResMf. Furthermore, miR-183/96/182 regulates the number of corneal ResMf. Inactivation of miR-183/96/182 in mouse results in more steady-state corneal resident immune cells, including ResMf, and leads to a simultaneous early upregulation of innate IL-17f and IL-10 production in the cornea after Pseudomonas aeruginosa infection. Its multiplex regulations on the simultaneous production of IL-17f and IL-10, TLR4 signaling pathway and the number of corneal ResMf place miR-183/96/182 in the center of corneal innate immunity, which is key to the homeostasis of the cornea, ocular immune privilege, and the corneal response to microbial infections. ImmunoHorizons, 2020, 4: 729-744.

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Section: Resultssupporting

confidence: 87%

The miR-183/96/182 Cluster Regulates the Functions of Corneal Resident Macrophages

et al. 2020

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“…In the previous studies, miR-182-5p was reported to function as a tumor suppressor of cancer metastasis through regulating RAB27A, FOXO3a, ARRDC3, PTEN and Cofilin 1 18–21. Dysregulated miR-182-5p was also involved in nonalcoholic steatohepatitis, chondrogenesis, lupus nephritis and cerebral ischemia-reperfusion injury 23–26. Several studies also indicated that miR-128-3p was down-regulated in several types of cancer, and restoration of miR-128-3p inhibited cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Noncoding RNA SNHG16 Sponges miR-182-5p And miR-128-3p To Promote Retinoblastoma Cell Migration And Invasion By Targeting LASP1</p>

Yang¹,

Zhang²,

Lu³

et al. 2019

OTT

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BackgroundLong noncoding RNAs (lncRNAs) are dysregulated and play an important role in the tumorigenesis and progression of cancers. However, the potential roles of SNHG16 in retinoblastoma progression still remain largely unclear.Materials and methodsThe expression levels of SNHG16, miR-182-5p, miR-128-3p and LASP1 in retinoblastoma tissues and cell lines were detected using qRT-PCR. The migratory and invasive abilities of retinoblastoma cells were assessed using Transwell assay. The regulatory relationships among SNHG16, miR-182-5p, miR-128-3p and LASP1 were analyzed through bioinformatics prediction and validated by luciferase reporter assay and Western blot.ResultsHere, we demonstrated that SNHG16 was frequently up-regulated in retinoblastoma tissue samples and cell lines. Clinicopathological features showed that high levels of SNHG16 were significantly associated with retinoblastoma metastasis and predicted poor overall survival. Functional studies demonstrated that knockdown of SNHG16 suppressed retinoblastoma cell migration and invasion. Mechanistic investigation revealed that SNHG16 exerted its oncogenic activity through increasing LASP1 expression and sponging miR-182-5p and miR-128-3p.ConclusionTaken together, our findings suggest SNHG16 as a novel biomarker and therapeutic target against retinoblastoma.

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“…Many microRNAs, such as miR-130a, miR-132, and miR-143, are directly implicated in BBB breakdown. 6,9,40 Several studies have confirmed that miR-182 affects cerebral ischemia injury by targeting inhibitory members of the iASPP family and toll-like receptor 4. 12,41 In our experiments, we found for the first time that miR-182 was upregulated during cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐182 exacerbates blood‐brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia

Zhang

Tian

et al. 2020

FASEB j.

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Cerebral ischemia causes damage to the structure and function of the blood‐brain barrier (BBB) and alleviating BBB destruction will be of great significance for the treatment and prognosis of ischemic stroke. Recently, microRNAs have been shown to play a critical role in BBB integrity. However, the potential mechanism by which microRNA‐182 (miR‐182) affects the BBB in ischemic stroke remains unclear. We demonstrated for the first time that cerebral ischemia leads to a significant progressive increase in miR‐182 after pMCAO, and bEnd.3 cells are the primary target cells of miR‐182. In miR‐182 KD transgenic mice, infarct volume, and BBB permeability were attenuated, and tight junction (TJ) proteins increased. Inhibition of miR‐182 with an antagomir reduced OGD‐induced apoptosis of bEnd.3 cells and the loss of ZO‐1 and Occludin. To further explore the mechanism by which miR‐182 regulates BBB integrity, we detected the apoptotic proteins Bcl‐2/Bax and demonstrated that mTOR and FOXO1 were the targets of miR‐182. Inhibition of mTOR/FOXO1 by rapamycin/AS1842856 decreased the ratio of Bcl‐2/Bax and exacerbated TJ protein loss. Taken together, inhibition of miR‐182 protects BBB integrity by reducing endothelial cell apoptosis through the mTOR/FOXO1 pathway. Thus, miR‐182 may be a potential target for the treatment of BBB disruption during cerebral ischemia.

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MicroRNA-182-5p attenuates cerebral ischemia-reperfusion injury by targeting Toll-like receptor 4

Cited by 68 publications

References 23 publications

The miR-183/96/182 Cluster Regulates the Functions of Corneal Resident Macrophages

The miR-183/96/182 Cluster Regulates the Functions of Corneal Resident Macrophages

<p>Long Noncoding RNA SNHG16 Sponges miR-182-5p And miR-128-3p To Promote Retinoblastoma Cell Migration And Invasion By Targeting LASP1</p>

MicroRNA‐182 exacerbates blood‐brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia

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