» Articles » PMID: 31551710

Long Non-coding RNA TUG1 Sponges Mir-145a-5p to Regulate Microglial Polarization After Oxygen-Glucose Deprivation

Overview
Specialty Molecular Biology
Date 2019 Sep 26
PMID 31551710
Citations 42
Authors
Affiliations
Soon will be listed here.
Abstract

Microglia plays a critical role in neuroinflammation after ischemic stroke by releasing diverse inflammatory cytokines. Long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is widely expressed in adult brain and has been reported to participate in multiple biological processes associated with nervous system diseases. However, the role of TUG1 in microglial activation remains unidentified. BV-2 microglial cells were cultured and TUG1 siRNA was used to knock down its RNA level. Microglial cells were subjected to oxygen-glucose deprivation (OGD) for 4 h following TUG1 siRNA or scramble siRNA transient transfection. After 24 h reoxygenation, TUG1 level and microglial M1/M2 phenotype, as well as releasing inflammatory cytokines and their role to viability of SH-SY5Y neuroblastoma cells were determined by quantitative real-time PCR (qRT-PCR), ELISA, immunofluorescence and western blot. In addition, miR-145a-5p, a putative microRNA to bind with TUG1 by bioinformatics analysis, was simultaneously examined, then the interaction of TUG1 with miR-145a-5p and the potential involvement of NF-κB pathway were further evaluated by RNA-RNA pull-down assay and western blot. The cellular level of TUG1 was transiently up-regulated in microglial cells 24 h after OGD treatment, with an inverse correlation to downregulated miR-145a-5p. TUG1 knockdown drove microglial M1-like to M2-like phenotypic transformation with reduced production of pro-inflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) and incremental release of anti-inflammatory cytokine (interleukin-10, IL-10), as a result, promoted the survival of SH-SY5Y cells. Meanwhile, TUG1 knockdown prevented OGD-induced activation of NF-κB pathway as well, represented by decreased ratios of p-p65/p65 and p-IκBα/IκBα proteins. Furthermore, we found that TUG1 could physically bind to miR-145a-5p while miR-145a-5p inhibitor abolished the protective effects of TUG1 knockdown through activation of NF-κB pathway, suggesting a negative interaction between TUG1 and miR-145a-5p. Our study demonstrated that lncRNA TUG1, sponging miR-145a-5p with negative interaction, could regulate microglial polarization and production of inflammatory cytokines at a relatively early stage after OGD insult, where NF-κB pathway might be involved, possibly providing a promising therapeutic target against inflammatory injury.

Citing Articles

LncRNAs Orchestrating Neuroinflammation: A Comprehensive Review.

Esmaeili A, Yazdanpanah N, Rezaei N Cell Mol Neurobiol. 2025; 45(1):21.

PMID: 40056236 PMC: 11890384. DOI: 10.1007/s10571-025-01538-0.


Exosomes and non-coding RNAs: bridging the gap in Alzheimer's pathogenesis and therapeutics.

Chunhui G, Yanqiu Y, Jibing C, Ning L, Fujun L Metab Brain Dis. 2025; 40(1):84.

PMID: 39754674 PMC: 11700052. DOI: 10.1007/s11011-024-01520-7.


Epigenetic regulation of the inflammatory response in stroke.

Liang J, Yang F, Li Z, Li Q Neural Regen Res. 2024; 20(11):3045-3062.

PMID: 39589183 PMC: 11881735. DOI: 10.4103/NRR.NRR-D-24-00672.


Transplantation of miR-145a-5p modified M2 type microglia promotes the tissue repair of spinal cord injury in mice.

Li P, Zhao J, Ma Y, Wang L, Liang S, Fan F J Transl Med. 2024; 22(1):724.

PMID: 39103885 PMC: 11302162. DOI: 10.1186/s12967-024-05492-1.


Non-Coding RNA in Microglia Activation and Neuroinflammation in Alzheimer's Disease.

He C, Li Z, Yang M, Yu W, Luo R, Zhou J J Inflamm Res. 2023; 16:4165-4211.

PMID: 37753266 PMC: 10519213. DOI: 10.2147/JIR.S422114.


References
1.
Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

2.
Young T, Matsuda T, Cepko C . The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol. 2005; 15(6):501-12. DOI: 10.1016/j.cub.2005.02.027. View

3.
Wilusz J, Sunwoo H, Spector D . Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009; 23(13):1494-504. PMC: 3152381. DOI: 10.1101/gad.1800909. View

4.
Liu N, Chen N, Cui R, Li W, Li Y, Wei R . Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol. 2012; 13(6):633-41. DOI: 10.1016/S1470-2045(12)70102-X. View

5.
Rinn J, Chang H . Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012; 81:145-66. PMC: 3858397. DOI: 10.1146/annurev-biochem-051410-092902. View