{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:32:28Z","timestamp":1777527148376,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nanning Qingxiu District Science and Technology Project","award":["2019026"],"award-info":[{"award-number":["2019026"]}]},{"name":"Nanning Qingxiu District Science and Technology Project","award":["81960126"],"award-info":[{"award-number":["81960126"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019026"],"award-info":[{"award-number":["2019026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960126"],"award-info":[{"award-number":["81960126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computational and Mathematical Methods in Medicine"],"published-print":{"date-parts":[[2022,10,14]]},"abstract":"<jats:p>Acute pancreatitis (AP) is mainly caused by acinar cells releasing various inflammatory factors, causing inflammatory storms and leading to severe pancreatitis. Detection methods and treatment targets for pancreatitis are lacking, raising the urgency of identifying diagnostic markers and therapeutic targets for AP. MicroRNAs (miRNAs) have recently been identified as molecular markers for various biological processes such as tumors, immunity, and metabolism, and the involvement of miRNAs in inflammatory responses has been increasingly studied. To explore the role of miRNAs in AP is the primary objective of this study. By using qPCR on our cerulein-induced pancreatitis cell model, it is worth noting that the change of miR-146a-5p expression in inflammation-related miRNAs in AP was predominant. Next, ELISA, CCK8, and flow cytometry were used to inspect the impact of miR-146a-5p on pancreatitis. BiBiServ bioinformatics anticipated binding ability of miR-146a-5p and 3<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mo>\u2032<\/a:mo>\n                     <\/a:math>\n                  <\/jats:inline-formula>-untranslated region (3<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mo>\u2032<\/c:mo>\n                     <\/c:math>\n                  <\/jats:inline-formula>UTR) of TNF receptor-associated factor 6 (TRAF6), and the dual-luciferase assay verified the combination of the two. TRAF6 knockdown verified the effect of TRAF6 on the progression of pancreatitis. Finally, rescue experiments verified the capability of miR-146a-5p and TRAF6 interaction on the Toll-like receptor 9 (TLR9)\/NOD-like receptor protein 3 (NLRP3) signaling pathway and cell function. The expression of miR-146a-5p decreased in cerulein-induced AR42J pancreatic acinar cells. Functional experiments verified that miR-146a-5p facilitated the proliferation of AR42J pancreatic acinar cells and inhibited their apoptosis. Bioinformatic predictions and dual-luciferase experiments verified the actual binding efficiency between miR-146a-5p and 3<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mo>\u2032<\/e:mo>\n                     <\/e:math>\n                  <\/jats:inline-formula>UTR of TRAF6. Our study confirmed that knockdown of TRAF6 restrained the progression of pancreatitis, and knockdown of TRAF6 rescued pancreatitis caused by miR-146a-5p downregulation by the TLR9\/NLRP3 signaling pathway. Therefore, downregulation of miR-146a-5p in the induced pancreatitis cell model promotes the progression of pancreatitis via the TLR9\/TRAF6\/NLRP3 signaling pathway. There is potential for miR-146a-5p to serve as a diagnostic marker and therapeutic nucleic acid drug for AP.<\/jats:p>","DOI":"10.1155\/2022\/1747470","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T20:50:24Z","timestamp":1665780624000},"page":"1-11","source":"Crossref","is-referenced-by-count":4,"title":["Downregulation of miR-146a-5p Promotes Acute Pancreatitis through Activating the TLR9\/NLRP3 Signaling Pathway by Targeting TRAF6 In Vitro Rat Model"],"prefix":"10.1155","volume":"2022","author":[{"given":"Dehai","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biwei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5348-0130","authenticated-orcid":true,"given":"Zhihai","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"issue":"2","key":"1","first-page":"55","article-title":"Recurrent hypertriglyceridemic pancreatitis (HTGP); and the use of insulin drip as treatment","volume":"169","author":"T. Tran","year":"2017","journal-title":"The Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1139\/o89-075"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29212"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-016-1570-2"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3261-9"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8151"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1474995"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113992"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01455"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.007"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00276"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.149"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1111\/nep.12785"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.03.041"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147228"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1546-7"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700175"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401850"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0270-8"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.20317"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.11.081"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202012_24177"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.2174\/2211536607666180402120806"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202466"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2843"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12030478"},{"issue":"6","key":"28","first-page":"2379","article-title":"Two-layer regulation of <i>TRAF6<\/i> mediated by both TLR4\/NF-kB signaling and miR-589-5p increases proinflammatory cytokines in the pathology of severe acute pancreatitis","volume":"12","author":"Z. Chen","year":"2020","journal-title":"American Journal of Translational Research"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1038\/nature14191"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.5.C1295"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15499"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01522-6"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.7150\/thno.40566"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2020.06.016"}],"updated-by":[{"DOI":"10.1155\/2023\/9820687","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"record-id":"59871"},{"DOI":"10.1155\/2023\/9820687","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000}}],"container-title":["Computational and Mathematical Methods in Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/cmmm\/2022\/1747470.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/cmmm\/2022\/1747470.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/cmmm\/2022\/1747470.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T20:50:31Z","timestamp":1665780631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/cmmm\/2022\/1747470\/"}},"subtitle":[],"editor":[{"given":"Min","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":34,"alternative-id":["1747470","1747470"],"URL":"https:\/\/doi.org\/10.1155\/2022\/1747470","relation":{"retraction":[{"id-type":"doi","id":"10.1155\/2023\/9820687","asserted-by":"object"}]},"ISSN":["1748-6718","1748-670X"],"issn-type":[{"value":"1748-6718","type":"electronic"},{"value":"1748-670X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10,14]]}}}