PMID- 34268386 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220902 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 9 DP - 2021 May TI - LncRNA NEAT1 mediates intestinal inflammation by regulating TNFRSF1B. PG - 773 LID - 10.21037/atm-21-34 [doi] LID - 773 AB - 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-alpha). 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-kappaB p65 and p-NF-kappaB 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-kappaB 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-alpha stimulation increased NEAT1 and TNFRSF1B expression and activated NF-kappaB signaling pathway by increasing the translocation of NF-kappaB p65 to the nucleus. In the presence of TNF-alpha stimulation, NEAT1 knockdown reduces the expression of TNFRSF1B and the translocation of NF-kappaB 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 down-regulating 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-kappaB p65 translocation and mediates intestinal inflammation by regulating TNFRSF1B. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Pan, Shiyu AU - Pan S AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Liu, Rui AU - Liu R AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. FAU - Wu, Xing AU - Wu X AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Ma, Kejia AU - Ma K AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Luo, Weiwei AU - Luo W AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Nie, Kai AU - Nie K AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Zhang, Chao AU - Zhang C AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Meng, Xiangrui AU - Meng X AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Tong, Ting AU - Tong T AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Chen, Xuejie AU - Chen X AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Wang, Xiaoyan AU - Wang X AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, China. FAU - Deng, Minzi AU - Deng M AD - Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8246228 OTO - NOTNLM OT - NF-kappaB OT - Nuclear enriched abundant transcript 1 (NEAT1) OT - tumor necrosis factor superfamily member 1B (TNFRSF1B) OT - ulcerative colitis COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-34). The authors have no conflicts of interest to declare. EDAT- 2021/07/17 06:00 MHDA- 2021/07/17 06:01 PMCR- 2021/05/01 CRDT- 2021/07/16 06:42 PHST- 2021/01/06 00:00 [received] PHST- 2021/02/28 00:00 [accepted] PHST- 2021/07/16 06:42 [entrez] PHST- 2021/07/17 06:00 [pubmed] PHST- 2021/07/17 06:01 [medline] PHST- 2021/05/01 00:00 [pmc-release] AID - atm-09-09-773 [pii] AID - 10.21037/atm-21-34 [doi] PST - ppublish SO - Ann Transl Med. 2021 May;9(9):773. doi: 10.21037/atm-21-34.