ATP2B1-AS1 exacerbates sepsis-induced cell apoptosis and inflammation by regulating miR-23a-3p/TLR4 axis
Main Article Content
Keywords
apoptosis, ATP2B1-AS1, inflammation, miR-23a-3p, sepsis, TLR4
Abstract
Background: Sepsis is a life-threatening disease with dominant mortality. Its early diagnosis and treatment can improve prognosis and reduce mortality. Long noncoding RNAs (lncRNAs) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) is dysregulated and is involved in the progression of various diseases. Nevertheless, the role of ATP2B1-AS1 in sepsis remains unclear.
Methods: A human monocytic cell line, THP-1 cells, was stimulated to induce a model of sepsis in vitro. The levels of ATP2B1-AS1, miR-23a-3p, and TLR4 were assessed by real-time quantitative polymerase chain reaction. The role of ATP2B1-AS1 in cell apoptosis and inflammation was explored by flow cytometry, Western blot analysis and enzyme-linked immunosorbent serologic assay. The binding sites between ATP2B1-AS1 and miR-23a-3p, and between miR-23a-3p and TLR4 were predicted by BiBiServ and the Encyclopedia of RNA Interactomes (ENCORI) online sites, respectively, and confirmed by the luciferase assay.
Results: The level of ATP2B1-AS1 was increased in lipopolysaccharide (LPS)-treated THP-1 cells. LPS increased apoptosis ratio, relative protein expressions of pro-apoptotic factors, and relative messenger RNA (mRNA) level and concentrations of pro-inflammatory cytokines, but decreased the relative expression of anti-apoptosis protein and relative mRNA level and concentrations of anti-inflammatory factor. All these alterations were reversed with transfection of shATP2B1-AS1 into THP-1 cells. Moreover, ATP2B1-AS1 directly bound miR-23a-3p and negatively modulated the level of miR-23a-3p. Meanwhile, TLR4 was directly targeted by miR-23a-3p, and negatively and positively modulated by miR-23a-3p and ATP2B1-AS1, respectively.
Conclusion: ATP2B1-AS1 aggravated apoptosis and inflammation by modulating miR-23a-3p/TLR4 axis in LPS-treated THP-1 cells.
References
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21. Gai Y, Hao Y, Guo K. PIM2 promotes lung adenocarcinoma cell migration by regulating XIAP/NF-κB pathway. J Men Health (JOMH). 2021;17(3):153–9.
22. Fu Y, Jin R-R, Li Y-L, Luan H, Huang T, Zhao Y, et al. Isocorydine inhibits the proliferation of human endometrial carcinoma HEC-1B cells by downregulating the Ras/MEK/ERK signaling pathway. Eu J Gynaecol Oncol (EJGO). 2021;42(3):548–53. 10.31083/j.ejgo.2021.03.5225
23. Chhabra R, Rao S, Kumar BM, Shetty AV, Hegde AM, Bhandary M. Characterization of stem cells from human exfoliated deciduous anterior teeth with varying levels of root resorption. J Clin Pediatr Dent. 2021;45(2):104–11. 10.17796/1053-4625-45.2.6
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27. Xu L, Wang F. LINC00936 exacerbated myocardial infarction progression via miR-4795-3p/Wnt3a signaling pathway based on biological and imaging methods. Perfusion. 2022:2676591221076788. 10.1177/02676591221076788
28. Huang M, Cai S, Su J. The Pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20(21):5376. 10.3390/ijms20215376
29. Wu Z, Chen J, Zhao W, Zhuo CH, Chen Q. Inhibition of miR-181a attenuates sepsis-induced inflammation and apoptosis by activating Nrf2 and inhibiting NF-κB pathways via targeting SIRT1. Kaohsiung J Med Sci. 2021;37(3):200–7. 10.1002/kjm2.12310
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31. Gao Z, Huang D. lncRNA GAS5-mediated miR-23a-3p promotes inflammation and cell apoptosis by targeting TLR4 in a cell model of sepsis. Mol Med Rep. 2021;24(1):510. 10.3892/mmr.2021.12149
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35. Djuric O, Andjelkovic M, Vreca M, Skakic A, Pavlovic S, Novakovic I, et al. Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: Nested case-control study in a level-1 trauma centre in SERBIA. Injury. 2021;52(3):419–25. 10.1016/j.injury.2020.12.039
36. Rohsiswatmo R, Azharry M, Sari TT, Bahasoan Y, Wulandari D. TLR2 and TLR4 expressions in late-onset neonatal sepsis: Is it a potential novel biomarker? J Neonatal Perinatal Med. 2021;14(3):361–7. 10.3233/NPM-200411
37. Chen F, Zhu J, Wang W. Ulinastatin attenuates LPS-induced inflammation and inhibits endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells via regulation of the TLR4/NF-κB and Nrf2/HO-1 pathways. Inflammation. 2021;44(6):2323–32. 10.1007/s10753-021-01505-z
38. Zhang H, Lang W, Wang S, Li B, Li G, Shi Q. Echinacea polysaccharide alleviates LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of the TLR4/NF-κB signal pathway. Int Immunopharmacol. 2020;88:106974. 10.1016/j.intimp.2020.106974
39. Roy A, Srivastava M, Saqib U, Liu D, Faisal SM, Sugathan S, et al. Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways. Int Immunopharmacol. 2016;40:79–89. 10.1016/j.intimp.2016.08.026
40. Song C, Adili A, Kari A, Abuduhaer A. FSTL1 aggravates sepsis-induced acute kidney injury through regulating TLR4/MyD88/NF-κB pathway in newborn rats. Signa Vitae. 2021;17(3):167–73.
41. Ni WW, Zhang QM, Zhang X, Li Y, Yu SS, Wu HY, et al. Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model.Allergol Immunopathol (Madr). 2020;48(2):149–57. 10.1016/j.aller.2019.06.002
2. Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, et al. Incidence and mortality of hospital-and ICU-treated sepsis: Results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1552–62. 10.1007/s00134-020-06151-x
3. Mirijello A, Tosoni A, On Behalf of the Internal Medicine Sepsis Study G. New strategies for treatment of sepsis. Medicina (Kaunas). 2020;56(10):527. 10.3390/medicina56100527
4. Kim Y-J, Lee J-H, Lee S-W, Kim WY. Use of quick sequential organ failure assessment score-based sepsis clinical decision support system may be helpful to predict sepsis development. Signa Vitae. 2021;17(5):86–94.
5. Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318(13):1241–9. 10.1001/jama.2017.13836
6. Geisler S, Coller J. RNA in unexpected places: Long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol. 2013;14(11):699–712. 10.1038/nrm3679
7. Liao Y, Wang R, Wen F. Diagnostic and prognostic value of long noncoding RNAs in sepsis: A systematic review and meta--analysis. Expert Rev Mol Diagn. 2022:22(8):821–31. 10.1080/14737159.2022.2125801
8. Pierce JB, Zhou H, Simion V, Feinberg MW. Long Noncoding RNAs as therapeutic targets. Adv Exp Med Biol. 2022;1363: 161–75. 10.1007/978-3-030-92034-0_9
9. Szcześniak MW, Makałowska I. lncRNA–RNA interactions across the human transcriptome. PLoS One. 2016;11(3):e0150353. 10.1371/journal.pone.0150353
10. Chu Y, Wang X, Yu N, Li Y, Kan J. Long noncoding RNA FGD5-AS1/microRNA-133a-3p upregulates aquaporin 1 to decrease the inflammatory response in LPS-induced-sepsis. Mol Med Rep. 2021;24(5):784. 10.3892/mmr.2021.12424
11. Chen JX, Xu X, Zhang S. Silence of long noncoding RNA NEAT1 exerts suppressive effects on immunity during sepsis by promoting microRNA-125-dependent MCEMP1 downregulation. IUBMB Life. 2019;71(7):956–68. 10.1002/iub.2033
12. Han D, Fang R, Shi R, Jin Y, Wang Q. LncRNA NKILA knockdown promotes cell viability and represses cell apoptosis, autophagy and inflammation in lipopolysaccharide-induced sepsis model by regulating miR-140-5p/CLDN2 axis. Biochem Biophys Res Commun. 2021;559:8–14. 10.1016/j.bbrc.2021.04.074
13. Song KY, Zhang XZ, Li F, Ji QR. Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway. J Cell Mol Med. 2020;24(8):4466–79. 10.1111/jcmm.15105
14. Chodary Khameneh S, Razi S, Shamdani S, Uzan G, Naserian S. Weighted correlation network analysis revealed novel long non-coding RNAs for colorectal cancer. Sci Rep. 2022;12(1):2990. 10.1038/s41598-022-06934-w
15. Sheng X, Fan T, Jin X. Identification of key genes involved in acute myocardial infarction by comparative transcriptome analysis. Biomed Res Int. 2020;2020:1470867. 10.1155/2020/1470867
16. Wang L, Tan Y, Zhu Z, Chen J, Sun Q, Ai Z, et al. ATP2B1-AS1 promotes cerebral ischemia/reperfusion injury through regulating the miR-330-5p/TLR4-MyD88-NF-κB signaling pathway. Front Cell Dev Biol. 2021;9:720468. 10.3389/fcell.2021.720468
17. Ren Z, Wang X. Long non-coding ribonucleic acid ATP2B1-AS1 modulates endothelial permeability through regulating the miR-4729-IQGAP2 axis in diabetic retinopathy. J Diabetes Investig. 2022;13(3):443–52. 10.1111/jdi.13740
18. Shu C, Wang W, Wu L, Qi C, Yan W, Lu W, et al. LINC00936/microRNA-221-3p regulates tumor progression in ovarian-cancer by interacting with LAMA3. Recent Pat Anticancer Drug Discov. 2022. 10.2174/1574892817666220316152201. Epub ahead of print.
19. Xiao Q, Lu R, He C, Zhou K. Protective effect of USP22 against paraquat-induced lung injury via activation of SIRT1/NRF2 pathway. Signa Vitae. 2021;17(3):187–95.
20. Sun S, Yao M, Yuan L, Qiao J. Long-chain non-coding RNA n337374 relieves symptoms of respiratory syncytial virus--induced asthma by inhibiting dendritic cell maturation via the CD86 and the ERK pathway. Allergol Immunopathol (Madr). 2021;49(3):100–7. 10.15586/aei.v49i3.85
21. Gai Y, Hao Y, Guo K. PIM2 promotes lung adenocarcinoma cell migration by regulating XIAP/NF-κB pathway. J Men Health (JOMH). 2021;17(3):153–9.
22. Fu Y, Jin R-R, Li Y-L, Luan H, Huang T, Zhao Y, et al. Isocorydine inhibits the proliferation of human endometrial carcinoma HEC-1B cells by downregulating the Ras/MEK/ERK signaling pathway. Eu J Gynaecol Oncol (EJGO). 2021;42(3):548–53. 10.31083/j.ejgo.2021.03.5225
23. Chhabra R, Rao S, Kumar BM, Shetty AV, Hegde AM, Bhandary M. Characterization of stem cells from human exfoliated deciduous anterior teeth with varying levels of root resorption. J Clin Pediatr Dent. 2021;45(2):104–11. 10.17796/1053-4625-45.2.6
24. Yang Y, Yang L, Liu Z, Wang Y, Yang J. Long noncoding RNA NEAT 1 and its target microRNA-125a in sepsis: Correlation with acute respiratory distress syndrome risk, biochemical indexes, disease severity, and 28-day mortality. J Clin Lab Anal. 2020;34(12):e23509. 10.1002/jcla.23509
25. Geng F, Liu W, Yu L. Potential role of circulating long noncoding RNA MALAT1 in predicting disease risk, severity, and patients’ survival in sepsis. J Clin Lab Anal. 2019;33(8):e22968. 10.1002/jcla.22968
26. Xu Y, Shao B. Circulating long noncoding RNA ZNFX1 antisense RNA negatively correlates with disease risk, severity, inflammatory markers, and predicts poor prognosis in sepsis patients. Medicine (Baltimore). 2019;98(9):e14558. 10.1097/MD.0000000000014558
27. Xu L, Wang F. LINC00936 exacerbated myocardial infarction progression via miR-4795-3p/Wnt3a signaling pathway based on biological and imaging methods. Perfusion. 2022:2676591221076788. 10.1177/02676591221076788
28. Huang M, Cai S, Su J. The Pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20(21):5376. 10.3390/ijms20215376
29. Wu Z, Chen J, Zhao W, Zhuo CH, Chen Q. Inhibition of miR-181a attenuates sepsis-induced inflammation and apoptosis by activating Nrf2 and inhibiting NF-κB pathways via targeting SIRT1. Kaohsiung J Med Sci. 2021;37(3):200–7. 10.1002/kjm2.12310
30. Yang P, Han J, Li S, Luo S, Tu X, Ye Z. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2. Open Med (Wars). 2021;16(1):274–83. 10.1515/med-2021-0222
31. Gao Z, Huang D. lncRNA GAS5-mediated miR-23a-3p promotes inflammation and cell apoptosis by targeting TLR4 in a cell model of sepsis. Mol Med Rep. 2021;24(1):510. 10.3892/mmr.2021.12149
32. Zhao Z, Sun W, Guo Z, Zhang J, Yu H, Liu B. Mechanisms of lncRNA/microRNA interactions in angiogenesis. Life Sci. 2020;254:116900. 10.1016/j.lfs.2019.116900
33. Sun Q, Wang B, Li M. MicroRNA-23a-3p targeting of HMGB1 inhibits LPS-induced inflammation in murine macrophages in vitro. Exp Ther Med. 2022;23(5):322. 10.3892/etm.2022.11251
34. Liu Y, Hu R, Zhu J, Nie X, Jiang Y, Hu P, et al. The lncRNA PAHRF functions as a competing endogenous RNA to regulate MST1 expression by sponging miR-23a-3p in pulmonary arterial hypertension. Vascul Pharmacol. 2021;139:106886. 10.1016/j.vph.2021.106886
35. Djuric O, Andjelkovic M, Vreca M, Skakic A, Pavlovic S, Novakovic I, et al. Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: Nested case-control study in a level-1 trauma centre in SERBIA. Injury. 2021;52(3):419–25. 10.1016/j.injury.2020.12.039
36. Rohsiswatmo R, Azharry M, Sari TT, Bahasoan Y, Wulandari D. TLR2 and TLR4 expressions in late-onset neonatal sepsis: Is it a potential novel biomarker? J Neonatal Perinatal Med. 2021;14(3):361–7. 10.3233/NPM-200411
37. Chen F, Zhu J, Wang W. Ulinastatin attenuates LPS-induced inflammation and inhibits endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells via regulation of the TLR4/NF-κB and Nrf2/HO-1 pathways. Inflammation. 2021;44(6):2323–32. 10.1007/s10753-021-01505-z
38. Zhang H, Lang W, Wang S, Li B, Li G, Shi Q. Echinacea polysaccharide alleviates LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of the TLR4/NF-κB signal pathway. Int Immunopharmacol. 2020;88:106974. 10.1016/j.intimp.2020.106974
39. Roy A, Srivastava M, Saqib U, Liu D, Faisal SM, Sugathan S, et al. Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways. Int Immunopharmacol. 2016;40:79–89. 10.1016/j.intimp.2016.08.026
40. Song C, Adili A, Kari A, Abuduhaer A. FSTL1 aggravates sepsis-induced acute kidney injury through regulating TLR4/MyD88/NF-κB pathway in newborn rats. Signa Vitae. 2021;17(3):167–73.
41. Ni WW, Zhang QM, Zhang X, Li Y, Yu SS, Wu HY, et al. Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model.Allergol Immunopathol (Madr). 2020;48(2):149–57. 10.1016/j.aller.2019.06.002
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