Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p

Abstract

Long noncoding RNAs have been demonstrated to play crucial roles in the pathogenesis of spinal cord injury (SCI). In this study, we aimed to explore the roles and underlying mechanisms of lncRNA X-inactive specific transcript (XIST) in SCI progression. SCI mice model was constructed and evaluated by the Basso–Beattie–Bresnahan method. The SCI cell model was constructed by treating BV2 cells with lipopolysaccharide (LPS). The levels of XIST and miR-219-5p were determined by the reverse transcription quantitative polymerase chain reaction. The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Protein levels were measured via western blot assay. Cell viability and apoptosis were evaluated by cell counting kit-8 assay and flow cytometry analysis, respectively. The relationship between XIST and miR-219-5p was analyzed by online tool starBase, dual-luciferase reporter assay, and RNA immunoprecipitation assay. As a result, the XIST level was enhanced and the miR-219-5p level was declined in the SCI mice model. XIST was also upregulated in LPS-induced BV2 cells. LPS treatment restrained BV2 cell viability and accelerated apoptosis and inflammatory response. XIST knockdown effectively weakened LPS-induced BV2 cell injury. miR-219-5p was identified as a target of XIST. Moreover, inhibition of miR-219-5p restored the impacts of XIST knockdown on cell viability, apoptosis, and inflammation in LPS-treated BV2 cells. In addition, LPS-induced XIST promoted the activation of the nuclear factor-κB (NF-κB) pathway by sponging miR-219-5p. In conclusion, XIST silencing promoted microglial cell viability and repressed apoptosis and inflammation by sponging miR-219-5p, thus promoting the recovery of SCI.

Non-coding RNA and n6-methyladenosine modification play crucial roles in neuropathic pain

“…LncRNA PVT1 is believed to target miR-186-5p/CXCL13/CXCR5 axis, and is responsible for neuropathic pain caused by overactivation of astrocytes . Sponging of miR-219-5p by lncRNA XIST inhibited the viability of microglia cells, thereby affecting neuropathic pain (Zhong et al, 2021). In recent studies, antisense lncRNAs were also found to affect neuropathic pain.…”

Research Progress of Long Non-coding RNAs in Spinal Cord Injury

“…The changes in the expression of these molecules led to the decrease of apoptosis rate [ 26 ]. Similarly, Zhong et al reported that LncRNA XIST knockout can affect the expression of apoptosis-related proteins through targeting miR-219-5p, thus reducing apoptosis in spinal cord injury rat models [ 27 ]. In addition, knockdown of lncRNA-XIST has a momentous protective effect on SCI recovery by suppressing apoptosis through miR-494/PTEN/PI3K/AKT signaling axis [ 28 ].…”

Potential value of differentially expressed circular RNAs derived from circulating exosomes in the pathogenesis of rat spinal cord injury

“…Recently, non-coding RNAs (ncRNAs), for example, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been identified as pivotal players in SCI (Kimura et al, 2021;. Of note, the knockdown of certain lncRNAs such as TUG1, XIST, and ZFAS1 has shown a beneficial effect on SCI development through mouse as well as rat model studies (Chen Y. et al, 2021;Wu et al, 2021;Zhong et al, 2021), indicating the functional involvement and preclinical significance of these ncRNAs in SCI.…”