PMID- 33774143 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 171 DP - 2021 Jun TI - LncRNA p21, downregulating miR-181b, aggravates neuropathic pain by upregulating Tnfaip1 and inhibit the AKT/CREB axis. PG - 150-161 LID - S0361-9230(21)00075-7 [pii] LID - 10.1016/j.brainresbull.2021.03.005 [doi] AB - Recently, there is evidence that long non-coding RNA p21 may play a regulatory role in the development of neuropathic pain (NPP), but it remains to be studied. In this study, we found that lncRNA p21 and tumor necrosis factor alpha-induced protein 1 (Tnfaip1) expression were up-regulated and miR-181b expression was down-regulated in lipopolysaccharide (LPS)-induced and activated BV-2 microglia. The results of flow cytometry and ELISA suggested that overexpression of lncRNA p21 or Tnfaip1 promoted apoptosis and inflammatory factors secretion, and miR-181b overexpression inhibited apoptosis and secretion of inflammatory factors. Luciferase reporter gene analysis validated the adsorption of miR-181b by lncRNA p21. In addition, the targeting relationship between miR-181b and Tnfaip1 was determined. Next, the up-regulation of lncRNA p21 and miR-181b was used as a reversal experiment, and the results suggested that the up-regulation of miR-181b attenuated the promoting effect of lncRNA p21 and Tnfaip1 on apoptosis and inflammatory response, which may be related to the activation of AKT/cAMP response element binding protein (CREB) axis. Finally, the rat model of SNL with lncRNA p21 knockdown was constructed, and the results of paw retraction mechanical threshold (PWMT) and paw retraction thermal latency (PWTL) measurements showed that knockdown of lncRNA p21 alleviated neuropathic pain in rats. In conclusion, our study found that the lncRNA p21/miR-181b/Tnfaip1 axis probably plays an important role in the progression of neuropathic pain, among which lncRNA p21 may become a new insight in the treatment of neuropathic pain. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Liu, Yan AU - Liu Y AD - Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China. FAU - Sun, Hai AU - Sun H AD - Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China. FAU - Sun, Yan AU - Sun Y AD - Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China. Electronic address: yansun@jlu.edu.cn. LA - eng PT - Journal Article DEP - 20210324 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Carrier Proteins) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (MIRN181 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (TNFAIP1 protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Apoptosis/physiology MH - Carrier Proteins/genetics/*metabolism MH - Cell Line MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Inflammation/genetics/*metabolism MH - Male MH - Mice MH - MicroRNAs/genetics/*metabolism MH - Microglia/metabolism MH - Neuralgia/genetics/*metabolism MH - Pain Threshold/physiology MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Long Noncoding/genetics/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - *Up-Regulation OTO - NOTNLM OT - Neuropathic pain OT - The AKT/CREB axis OT - Tnfaip1 OT - lncRNA p21 OT - miR-181b EDAT- 2021/03/29 06:00 MHDA- 2022/02/08 06:00 CRDT- 2021/03/28 20:40 PHST- 2020/10/28 00:00 [received] PHST- 2021/03/04 00:00 [revised] PHST- 2021/03/08 00:00 [accepted] PHST- 2021/03/29 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/03/28 20:40 [entrez] AID - S0361-9230(21)00075-7 [pii] AID - 10.1016/j.brainresbull.2021.03.005 [doi] PST - ppublish SO - Brain Res Bull. 2021 Jun;171:150-161. doi: 10.1016/j.brainresbull.2021.03.005. Epub 2021 Mar 24.