Long Non-coding RNA ANRIL Downregulation Alleviates Neuroinflammation in an Ischemia Stroke Model via Modulation of the miR-671-5p/NF-kappa B Pathway

作者全名："Deng, Ling; Jiang, Jin; Chen, Sha; Lin, Xing; Zuo, Tianrui; Hu, Qingwen; Wu, Yu; Fan, Xiaomei; Dong, Zhi"

作者地址："[Deng, Ling; Chen, Sha; Zuo, Tianrui; Hu, Qingwen; Wu, Yu; Fan, Xiaomei; Dong, Zhi] Chongqing Med Univ, Coll Pharmacol, Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Jiang, Jin] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Lin, Xing] Chongqing Univ, Dept Biol Immunotherapy, Canc Hosp, Chongqing 400030, Peoples R China"

通信作者："Dong, Z (通讯作者)，Chongqing Med Univ, Coll Pharmacol, Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000777280500002

JCR分区：Q2

影响因子：4.4

年份：2022

卷号：47

期号：7

开始页：2002

结束页：2015

文献类型：Article

关键词：Lnc RNA ANRIL; miR-671-5p; Ischemia stroke; Neuroinflammation; NF-kappa B; Tight junction disorder

摘要："The aim of this study was to investigate the role and underlying mechanism of the long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus, ANRIL) in ischemia stroke (IS) injury. Downregulation of ANRIL by right intracerebroventricular injected si-ANRIL in middle cerebral artery occlusion-reperfusion (MCAO/R) C57/BL6 mice and by transferring si-ANRIL in oxygen glucose deprivation/reperfusion (OGD/R) HT22 cells. The results showed that ANRIL levels increased in IS model, downregulation of ANRIL reduced infract area, neurological deficit scores and injured cells, and prolong fall latency time in MCAO/R mice, improved cell viability and reduced cell cytotoxicity in OGD/R cells. Fluorescence in Situ Hybridization detected that there were both ANRIL and miR-671-5p in neurons; miranda v3.3a and dual luciferase reporter assay demonstrated that miR-671-5p was one of direct target of ANRIL; and our previously published research demonstrated that NF-kappa B was one of direct target of miR-671-5p. Downregulation of ANRIL alleviated neuroinflammation and reduced p-NF-kappa B, NF-kappa B, pro-inflammatory cytokines (IL-1 beta, IL-6, TNF-a), and iNOS, which diminished by miR-671-5p antagomir both in in vivo and in vitro IS models. Downregulation of ANRIL alleviated disruption of blood brain barrier, and protected against tight junction (ZO-1, occludin and claudin 5) disorder in MCAO/R mice. This work clarified that downregulation of ANRIL reduced neuroinflammation by negatively regulating miR-671-5p to inhibit NF-kappa B in IS models, which provided a theoretical foundation for the protective effect of downregulating ANRIL for IS patients."

基金机构："Research Innovation of Graduate Students in Chongqing [CYB19165]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0325, cstc2019jcyjmsxmX0630]; Chinese Medicine Science and Technology project of Chongqing Municipal Health committee [2021ZY3794]; General Topics of Basic Research and Frontier Exploration of Yuzhong district, Chongqing [20210121]"

基金资助正文："This work was funded by Research Innovation of Graduate Students in Chongqing (CYB19165), Natural Science Foundation of Chongqing (cstc2019jcyjmsxmX0630), Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0325), Chinese Medicine Science and Technology project of Chongqing Municipal Health committee, Grand No. 2021ZY3794 and General Topics of Basic Research and Frontier Exploration of Yuzhong district, Chongqing (20210121)."