LncRNA NEAT1 promotes apoptosis and inflammation in LPS‑induced sepsis models by targeting miR‑590‑3p

Abstract

Sepsis is a complication of infection caused by disease or trauma. Increasing evidence have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of sepsis. However, the mechanism of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in the regulation of sepsis progression remains to be elucidated. Lipopolysaccharide (LPS) was used to induce a sepsis cell model. The expression levels of NEAT1 and microRNA (miR)-590-3p were determined by reverse transcription-quantitative PCR. Cell viability and apoptosis were detected using Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Western blot analysis was performed to evaluate the levels of apoptosis-and NF-κB signaling pathway-related proteins. The concentration of inflammatory cytokines was determined using ELISA. In addition, dual-luciferase reporter assay, RNA immunoprecipitation and biotin-labeled RNA pull-down assay were performed to verify the interaction between NEAT1 and miR-590-3p. The results showed that NEAT1 was highly expressed in patients with sepsis and LPS-induced H9c2 cells. Knockdown of NEAT1 decreased LPS-induced cell apoptosis and inflammation response in H9c2 cells. Meanwhile, miR-590-3p showed decreased expression in sepsis, and its overexpression could relieve LPS-induced H9c2 cell damage. Further experiments revealed that NEAT1 could sponge miR-590-3p. Knockdown of miR-590-3p reversed the inhibitory effect of NEAT1 knockdown on LPS-induced H9c2 cell damage. Additionally, the NEAT1/miR-590-3p axis could regulate the activity of the NF-κB signaling pathway. To conclude, lncRNA NEAT1 accelerated apoptosis and inflammation in LPS-stimulated H9c2 cells via sponging miR-590-3p. These findings may provide a new strategy for the treatment of sepsis.

Long non‑coding RNA NEAT1 promotes pulmonary fibrosis by regulating the microRNA‑455‑3p/SMAD3 axis

“…For example, NEAT1 was reported to be highly expressed in Parkinson's disease, and NEAT1 knockdown inhibited PD progression via regulating the miR-212-3p/axin 1 signaling pathway ( 24 ). NEAT1 also accelerated apoptosis and inflammation in lipopolysaccharide-induced sepsis models by targeting miR-590-3p ( 25 ). In the present study, NEAT1 was found to be upregulated in the TGF-β1-treated HPAEpiC and BEAS-2B cell lines, suggesting that the high expression level of NEAT1 could be associated with pulmonary fibrosis.…”

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

“…Apoptosis is essential for the selective elimination of cells, and it plays an important role in the occurrence and development of acute lung injury. The inhibition of lung cells apoptosis might increase the animal survival rate in LPS-induced acute lung injury [ 29 ]. DEX pretreatment ameliorated LPS-induced lung inflammation and oxidative stress by activating the Nrf2/Keap1 signaling pathway and regulating the expression of antioxidant genes [ 30 ].…”

Pseudogene HMGN2P46 as a microRNA sponge to regulate HMGN2 expression via competing for miR-590-3p in severe acute pancreatitis

“…Moreover, Ma et al (2019) reported that miR-590-3p inhibited TNFRAF-6 to attenuate acute kidney injury in septic mice. MiR-590-3p also inhibited the LPS-induced sepsis apoptosis and inflammation (Liu et al, 2020b). In our study, miR-590-3p as a sponge to regulate inflammatory response of SAP and we did not discuss the function of miR-590-3p alone in SAP inflammation.…”

“…MiRNAs lead to translation inhibition of a large number of genes by sequence-specific binding to the 3'untranslated regions (UTRs) of homologous mRNAs (Pu et al, 2019). It is reported that miR-590-3p is an interesting gene that play an exactly opposite effect in different cancers (Ge and Gong, 2017;Salem et al, 2018) and also have function in inflammation injury (Liu et al, 2020b). But there have been no related reports in SAP.…”