LncRNA CCAT1 Protects Astrocytes Against OGD/R-Induced Damage by Targeting the miR-218/NFAT5-Signaling Axis
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ORIGINAL RESEARCH
LncRNA CCAT1 Protects Astrocytes Against OGD/R‑Induced Damage by Targeting the miR‑218/NFAT5‑Signaling Axis Xun Xia1 · Hao Niu2 · Yuan Ma3 · Bo Qu4 · Mingjie He1 · Kai Yu1 · Enren Wang1 · Lie Zhang1 · Jianwen Gu5 · Gang Liu1 Received: 23 September 2019 / Accepted: 2 March 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords LncRNA CCAT1 · Apoptosis · Inflammatory responses · miR-218/NFAT5 axis
Introduction SCI is a serious central nervous system (CNS) trauma and commonly results in permanent and lifelong disabilities that reduce the quality of life and increase morbidity and mortality (Varma et al. 2013). To date, no effective treatments for Xun Xia and Hao Niu are coauthors and contributed equally to this work. * Jianwen Gu [email protected] Gang Liu [email protected] 1
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Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu 610500, Sichuan, People’s Republic of China Sichuan Institute of Computer Science, Chengdu 610041, Sichuan, People’s Republic of China
SCI exist (Silva et al. 2014). Thus, research into the mechanisms involved in SCI must be conducted to develop new therapeutic strategies to alleviate
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