Sepsis is a life-threatening condition and often associated with multiple organ failure. Nuclear-enriched abundant transcript 1 (NEAT1), a member of long non-coding RNAs (lncRNAs), was reported to be involved in the regulation of sepsis progression. However, its precise regulatory mechanism needs to be further explored.
CCK-8 assay was utilized to check cell viability. The qRT-PCR was employed to detect the expression levels of NEAT1, miR-370-3p and iIrak2. Flow cytometry assay and ELISA were used to check cell apoptosis and the concentrations of inflammatory cytokines, respectively. The starBase was used to predict binding sites between miR-370-3p and NEAT1 or Irak2 and the dual-luciferase reporter assay was performed to verify the interaction. The protein level of Irak2 in samples was measured by western blot.
The high concentration of lipopolysaccharide (LPS) led to the high death ratio of RAW 264.7 and HL-1 cells. Besides, NEAT1 and Irak2 were upregulated in sepsis tissues and LPS-induced RAW 264.7 and HL-1 cells, opposite to the expression of miR-370-3p. In addition, knockdown of NEAT1 promoted viability, suppressed apoptosis and reduced the expression of inflammatory cytokines in LPS-induced RAW 264.7 and HL-1 cells. Moreover, we found that miR-370-3p interacted with NEAT1 and targeted the 3’UTR of Irak2. Further research indicated that downregulation of miR-370-3p or upregulation of IraK2 rescued NEAT1 silencing-mediated inhibitory effect on sepsis progression.
Knockdown of NEAT1 hampered sepsis progression by downregulating Irak2 via interacting with miR-370-3p in LPS-induced RAW 264.7 and HL-1 cells.
© 2020. Published by The Company of Biologists Ltd.
About The Expert
Ting Xiao
Chuihua Sun
Ying Xiao
Yunbao Li
References
PubMed