LncRNA NEAT1 mediates intestinal inflammation by regulating TNFRSF1B

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal disease. Our previous work showed that long non-coding RNA (LncRNA) nuclear enriched abundant transcript 1 (NEAT1) plays an important role in IBD. In the current study, we aimed to explore the underlying mechanism by which NEAT1 participates in the development of the disease.Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of NEAT1 and tumor necrosis factor superfamily member 1B (TNFRSF1B) in clinical specimens and dextran sulfate sodium (DSS) colitis mice. Inflammatory cell models were established by stimulating human normal intestinal epithelial cell line NCM460 and human colon cancer cell line HT-29 with tumor necrosis factor alpha (TNF-α). Expressions of inflammatory cytokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) or RT-qPCR, TNFRSF1B, NF-κB p65 and p-NF-κB p65 followed by the knockdown or overexpression of NEAT1 and TNFRSF1B were analyzed by western blotting, and the regulatory effects of NEAT1 on TNFRSF1B were detected by RNA pull-down experiments and RNA-decay assay. The translocation of NF-κB p65 to the nucleus was detected by immunofluorescence.Results: In patients' specimens and DSS colitis mouse models, NEAT1 and TNFRSF1B expression were up-regulated compared with the control group. TNF-α stimulation increased NEAT1 and TNFRSF1B expression and activated NF-κB signaling pathway by increasing the translocation of NF-κB p65 to the nucleus. In the presence of TNF-α stimulation, NEAT1 knockdown reduces the expression of TNFRSF1B and the translocation of NF-κB p65, thereby relieves cell inflammation. These effects can be reversed by the overexpression of TNFRSF1B.In addition, NEAT1 is involved in inflammatory response by up-regulating the mRNA levels of TNFRSF1B, and knocking down NEAT1 can alleviate inflammation by downregulating TNFRSF1B. Moreover, NEAT1 co-precipitates TNFRSF1B mRNA in RNA-pulldown assay, and the presence of NEAT1 stabilizes the mRNA of TNFRSF1B.Conclusions: Our results showed that LncRNA NEAT1 promotes NF-κB p65 translocation and mediates intestinal inflammation by regulating TNFRSF1B.

Knockdown of long non‑coding RNA NEAT1 relieves inflammation of ulcerative colitis by regulating the miR‑603/FGF9 pathway

“…The present study aimed to investigate the differential expression of NEAT1 in UC progression and development. The results demonstrated that NEAT1 expression was upregulated in patients with UC compared with healthy individuals, which is consistent with the results of a study by Pan et al ( 37 ) in which LncRNA NEAT1 mediated intestinal inflammation by regulating TNFRSF1B. Mechanistically, inhibition of NEAT1 significantly decreased injury in FHCs treated with LPS.…”

Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer

“…Interestingly, NEAT1 can directly interact with mRNA to affect its stability without the participation of miRNA. NEAT1 can bind and stabilize TNFRSF1B mRNA, contributing to the NF-κB signaling pathway [ 127 ]. Feng et al [ 128 ] suggested that NEAT1 can also increase the stability of ELF3 mRNA by increasing its N6-methyladenosine (m6A) modification, promoting the proliferation and metastasis of pancreatic cancer.…”

Long Non-Coding RNAs as Biomarkers and Therapeutic Targets in Sepsis

“…CDKN2B-AS1 was found to enhance the function of intestinal barrier (130). In an LPS-induced intestinal inflammation model, seven core lncRNAs and their target genes were identified and analyzed using a co-expression network, which provided new insights into the pathological mechanism for intestinal inflammation (131). In another inflammatory cell model, NEAT1 was observed to promote the translocation of NF-kB p65, mediating intestinal inflammation by the regulation of TNF superfamily member 1B (132).…”

“…In an LPS-induced intestinal inflammation model, seven core lncRNAs and their target genes were identified and analyzed using a co-expression network, which provided new insights into the pathological mechanism for intestinal inflammation ( 131 ). In another inflammatory cell model, NEAT1 was observed to promote the translocation of NF-κB p65, mediating intestinal inflammation by the regulation of TNF superfamily member 1B ( 132 ). Knockdown of SNHG5, that could interact with miR-375/Janus kinase 2 axis, reduced the apoptosis and promoted the proliferation of mouse colon cells ( 133 ).…”