Abstract
Spinal cord injury (SCI) is a grievous neurology-related disorder that causes many devastating symptoms. Emerging roles of long non-coding RNAs (lncRNA) have been shown to play critical roles in multiple neurological diseases. This research planned to dig the function and latent molecular mechanisms of the lncRNA CCAT1 on OGD/R-disposed injury in astrocytes. We observed that CCAT1 expression was diminished and miR-218 expression was elevated in astrocytes during OGD/R. Additionally, an abundance of CCAT1 obviously amplified cell viability and restrained OGD/R-triggered apoptosis in astrocytes, as characterized by reduced levels of pro-apoptotic proteins Bax and C-caspase-3, concomitant with elevated level of anti-apoptotic Bcl-2 protein. Furthermore, administration of CCAT1 remarkably mitigated OGD/R injury-induced neuro-inflammatory responses, reflected in a reduction of inflammatory cytokines including TNF-α, IL-1β, and IL-6. In action, CCAT1 served as an endogenous sponge effectively downregulating miR-218 expression by binding directly to it, and a negative regulatory relationship between miR-218 and NFAT5. Mechanistically, introduction of miR-218 reversed the inhibitory effects of CCAT1 on OGD/R-induced apoptosis and inflammation damage, which directly resulted from the inhibition of miR-218 and its targeting of NFAT5. Collectively, our study illuminated a new CCAT1/miR-218/NFAT5 regulatory axis in which CCAT1 served as a competing endogenous RNA by sponging miR-218, effectively upregulating NFAT5 expression, thereby alleviating apoptosis and inflammation damage under OGD/R condition. CCAT1 is, therefore, a putative therapeutic target for SCI, based on the results of this study and the potential application of CCAT1 as a neuroprotective agent.
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XX, HN, YM, JWG and GL: Conception, design, and development of methodology; XX, HN, BQ, MJH, KY, ERW and GL: Acquisition of data, analysis, and interpretation of data; LZ and JWG: Contribution new reagents or analytic tools; XX, HN, YM, BQ, MJH and JWG: Study supervision, manuscript writing, and manuscript revision. All authors read and approved the final version.
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Xia, X., Niu, H., Ma, Y. et al. LncRNA CCAT1 Protects Astrocytes Against OGD/R-Induced Damage by Targeting the miR-218/NFAT5-Signaling Axis. Cell Mol Neurobiol 40, 1383–1393 (2020). https://doi.org/10.1007/s10571-020-00824-3
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DOI: https://doi.org/10.1007/s10571-020-00824-3