LncRNA RMST activates TAK1-mediated NF-κB signaling and promotes activation of microglial cells via competitively binding with hnRNPK.

Abstract

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.

• Authors: Xiu-Lan Sun, Zhao-Lu Wang, Qian Wu, Shan-Quan Jin, Juan Yao, Hong Cheng
• Journal: IUBMB life (IUBMB Life) Vol. 71 Issue 11 Pg. 1785-1793 (11 2019) ISSN: 1521-6551 [Electronic] England
• PMID: 31329361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 International Union of Biochemistry and Molecular Biology.

Chemical References

• HNRNPK protein, mouse
• Heterogeneous-Nuclear Ribonucleoprotein K
• NF-kappa B
• RNA, Long Noncoding
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7
• Glucose
• Oxygen

Topics

• Animals
• Apoptosis
• Cells, Cultured
• Glucose (deficiency)
• Heterogeneous-Nuclear Ribonucleoprotein K (genetics, metabolism)
• MAP Kinase Kinase Kinases (genetics, metabolism)
• Mice
• Microglia (metabolism, pathology)
• NF-kappa B (genetics, metabolism)
• Neurons (metabolism, pathology)
• Oxygen (metabolism)
• RNA, Long Noncoding (genetics)
• Signal Transduction