LncRNA RMST contributes to neuroinflammation after traumatic brain injury by targeting miR-139-5p.

Abstract

Introduction: Neuroinflammation plays a significant role in the pathological progression of traumatic brain injury (TBI) and represents a promising therapeutic target. The present study focused on exploring the mechanism of long noncoding RNA rhabdomyosarcoma 2 associated transcripts (RMST) in TBI-induced neuroinflammation.

Material and methods: Controlled cortex injury was constructed as an in vivo TBI rat model and lipopolysaccharide (LPS)-induced microglia BV2 was constructed as an in vitro cellular model. Reverse transcription-quantity polymerase chain reaction (RT-qPCR) was employed to detect RMST levels in cerebral cortical tissues and BV2 cells. The modified neurological severity score (mNSS) and Morris water maze test were used to analyze neurological deficits and cognitive dysfunction. Enzyme-linked immunosorbent assay (ELISA) assay and flow cytometry were conducted to examine inflammatory factor levels and apoptosis. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the target relationship between microRNA (miR)-139-5p and RMST.

Results: RMST was present at high levels in TBI cerebral cortex tissues and LPS-induced BV2 cells, while miR-139-5p was reduced compared with the sham. Silencing RMST alleviated neurological deficits and cognitive dysfunction in TBI rats, but this alleviation was partially eliminated by the reduction of miR-139-5p. Additionally, overactivated neuroinflammatory factors in the TBI cerebral cortex were also suppressed by the knockdown of RMST, but partially restored by reduced miR-139-5p. Finally, the promotion of apoptosis and inflammatory mediator secretion of BV2 by LPS was diminished by silencing of RMST. These effects were all partially attenuated by silencing of miR-139-5p.

Conclusions: RMST can aggravate neuroinflammation and apoptosis in microglia after TBI and thereby affect neurological dysfunction by regulating miR-139-5p.