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LncRNA RMST activates TAK1‐mediated NF‐κB signaling and promotes activation of microglial cells via competitively binding with hnRNPK
Author(s) -
Sun XiuLan,
Wang ZhaoLu,
Wu Qian,
Jin ShanQuan,
Yao Juan,
Cheng Hong
Publication year - 2019
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2125
Subject(s) - gene knockdown , signal transduction , microbiology and biotechnology , cancer research , biology , chemistry , apoptosis , biochemistry
This study aimed to explore the biological role and molecular mechanism of long noncoding RNA (lncRNA) rhabdomyosarcoma 2‐associated transcript (RMST) in regulating microglial activation. Mouse microglial BV2 cells were cultured to establish the cell model of cerebral ischemic stroke by oxygen–glucose deprivation (OGD). We observed highly expressed RMST, increased expression of M1, and decreased expression of M2 markers in BV2 microglial cells stimulated with OGD. These alterations were reversed by RMST knockdown. Activation of transforming growth factor‐beta‐activated kinase 1 (TAK1)‐mediated nuclear factor‐κB (NF‐κB) pathway was observed upon OGD stimulation, which was promoted by RMST through competitively binding with heterogeneous nuclear ribonucleoprotein K (hnRNPK), confirmed by RNA pull down and RNA immunoprecipitation (RIP) assays. Furthermore, RMST overexpressing‐BV2 cells effectively enhanced neuronal apoptosis. In conclusion, RMST promoted OGD‐induced microglial M1 polarization by competitively interacting with hnRNPK via TAK1‐mediated NF‐κB pathway, which will provide a basis for understanding the pathogenesis of cerebrovascular diseases.