Abstract
BackgroundSpinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development.MethodsUsing in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique.ResultsWe revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation.ConclusionIn summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.
Highlights
Spinal cord injury (SCI) is, in most cases, caused by trauma and is associated with health burden both at personal and societal levels [1, 2]
Lymphoid enhancer-binding factor 1 (LEF1)-AS1 upregulated in SCI models The well-established model of SCI was used to investigate the expression of Long non-coding RNAs (lncRNAs) LEF1-AS1 in SCI mode
The expression of a lncRNA LEF1-AS1 was significantly higher in the SCI animal model than in the sham group (P = 0.002, Fig. 1b)
Summary
Spinal cord injury (SCI) is, in most cases, caused by trauma and is associated with health burden both at personal and societal levels [1, 2]. SCI is characterized by a primary mechanical insult to the spinal cord and subsequently causes secondary injury. Secondary injury may instigate apoptotic and necrotic cell death and excessive inflammatory response [4]. Inflammatory cytokines induce microglial cells, and apoptosis is mainly used in the pathogenesis of SCI [5]. Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. To comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
