{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:06:14Z","timestamp":1783721174104,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772210"],"award-info":[{"award-number":["81772210"]}],"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":["31470277"],"award-info":[{"award-number":["31470277"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005225","name":"Construct Program of the Key Discipline in Hunan Province","doi-asserted-by":"publisher","award":["2011-76"],"award-info":[{"award-number":["2011-76"]}],"id":[{"id":"10.13039\/501100005225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Long non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in many diseases. However, few studies have shown that lncRNAs take part in the pathogenesis of <jats:italic>Chlamydia trachomatis<\/jats:italic> (<jats:italic>C. trachomatis<\/jats:italic>). Here, we used a lncRNA microarray to detect the global lncRNA expression profiles in HeLa cells transfected with pORF5 plasmid protein, an important virulence factor for <jats:italic>C. trachomatis<\/jats:italic>. The differentially expressed lncRNAs and mRNAs screened by microarray were selected for validation by quantitative real-time PCR. The up-regulated lncRNA zinc finger antisense 1 (ZFAS1) was presumed to involved in MAPK pathways by bioinformatics analysis. Inhibition of ZFAS1 decreased the apoptotic rate of pORF5 and reduced the infectivity of <jats:italic>C. trachomatis<\/jats:italic>, and MAPK\/p38 pathway was involved in anti-apoptotic effect induced by ZFAS1. Therefore, the present study confirmed that pORF5 up-regulates ZFAS1 to promote host cell survival via MAPK\/p38 pathway and influences the infectivity of <jats:italic>C. trachomatis.<\/jats:italic><\/jats:p>","DOI":"10.3389\/fmicb.2020.593295","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T22:35:22Z","timestamp":1610058922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Chlamydia trachomatis Plasmid Protein pORF5 Up-Regulates ZFAS1 to Promote Host Cell Survival via MAPK\/p38 Pathway"],"prefix":"10.3389","volume":"11","author":[{"given":"Yating","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzhen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanhua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengmei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiulin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010256","article-title":"Chlamydial intracellular survival strategies.","volume":"3","author":"Bastidas","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B2","first-page":"20368","article-title":"Chlamydial plasmid-encoded protein pORF5 induces production of IL-1beta and IL-18 via NALP3 inflammasome activation and p38 MAPK pathway.","volume":"8","author":"Cao","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/cbf.3288","article-title":"Serine peptidase inhibitor Kazal type I (SPINK1) promotes BRL-3A cell proliferation via p38, ERK, and JNK pathways.","volume":"35","author":"Chang","year":"2017","journal-title":"Cell Biochem. Funct."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6017","DOI":"10.1128\/jb.00847-10","article-title":"Characterization of Pgp3, a Chlamydia trachomatis plasmid-encoded immunodominant antigen.","volume":"192","author":"Chen","year":"2010","journal-title":"J. Bacteriol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01412","article-title":"Clear victory for chlamydia: the subversion of host innate immunity.","volume":"10","author":"Chen","year":"2019","journal-title":"Front. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"6405","DOI":"10.3892\/mmr.2018.8707","article-title":"Downregulation of the long non-coding RNA ZFAS1 is associated with cell proliferation, migration and invasion in breast cancer.","volume":"17","author":"Fan","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.gene.2019.01.025","article-title":"Expression of the lncRNA ZFAS1 in cervical cancer and its correlation with prognosis and chemosensitivity.","volume":"696","author":"Feng","year":"2019","journal-title":"Gene"},{"key":"B8","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1159\/000493265","article-title":"Long non-coding RNA ZEB1-Antisense 1 affects cell migration and invasion of cervical cancer by regulating epithelial-mesenchymal transition via the p38MAPK signaling pathway.","volume":"84","author":"Gan","year":"2019","journal-title":"Gynecol. Obstet. Invest."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01111","article-title":"Translated long non-coding ribonucleic acid ZFAS1 promotes cancer cell migration by elevating reactive oxygen species Production in hepatocellular carcinoma.","volume":"10","author":"Guo","year":"2019","journal-title":"Front. Genet."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23317","article-title":"Long noncoding RNAs in osteosarcoma via various signaling pathways.","volume":"34","author":"Han","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"B11","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.micinf.2018.06.003","article-title":"Chlamydial plasmid-encoded virulence factor Pgp3 interacts with human cathelicidin peptide LL-37 to modulate immune response.","volume":"21","author":"Hou","year":"2019","journal-title":"Microbes Infect."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1007\/s00284-018-1439-7","article-title":"Cervical cancer induction enhancement potential of chlamydia trachomatis: a systematic review.","volume":"75","author":"Karim","year":"2018","journal-title":"Curr. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1160\/th09-02-0128","article-title":"Proliferative stimulation of the vascular Endothelin-1 axis in vitro and ex vivo by infection with Chlamydia pneumoniae.","volume":"102","author":"Kern","year":"2009","journal-title":"Thromb. Haemost."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031102","article-title":"Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity.","volume":"21","author":"Lee","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx111","article-title":"Chlamydia trachomatis plasmid-encoded protein pORF5 protects mitochondrial function by inducing mitophagy and increasing HMGB1 expression.","volume":"75","author":"Lei","year":"2017","journal-title":"Pathog Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.bbrc.2019.01.005","article-title":"Long non-coding PCED1B-AS1 regulates macrophage apoptosis and autophagy by sponging miR-155 in active tuberculosis.","volume":"509","author":"Li","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3415","DOI":"10.1128\/iai.01377-07","article-title":"The chlamydial plasmid-encoded protein pgp3 is secreted into the cytosol of Chlamydia-infected cells.","volume":"76","author":"Li","year":"2008","journal-title":"Infect. Immun."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1473-8","article-title":"Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124\/STAT3 axis.","volume":"38","author":"Li","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.01029","article-title":"Long noncoding RNA lncGNAT11 inhibits gastric cancer cell proliferation and invasion through the Wnt\/betacatenin pathway in Helicobacter pylori infection.","volume":"11","author":"Liu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B20","article-title":"Correction to: the regulatory ZFAS1\/miR-150\/ST6GAL1 crosstalk modulates sialylation of EGFR via PI3K\/Akt pathway in T-cell acute lymphoblastic leukemia.","volume":"38","author":"Liu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2017.03.002","article-title":"Roles of LncRNAs in Viral Infections.","volume":"7","author":"Liu","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B22","article-title":"Anti-apoptotic activity of Chlamydia trachomatis Pgp3 protein involves activation of the ERK1\/2 pathway mediated by up-regulation of DJ-1 protein.","volume":"77","author":"Luo","year":"2020","journal-title":"Pathog. Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1016\/j.cellsig.2014.03.015","article-title":"Phosphorylation of heat shock protein 27 antagonizes TNF-alpha induced HeLa cell apoptosis via regulating TAK1 ubiquitination and activation of p38 and ERK signaling.","volume":"26","author":"Qi","year":"2014","journal-title":"Cell. Signal."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/genes8080206","article-title":"Viral infection identifies micropeptides differentially regulated in smORF-containing lncRNAs.","volume":"8","author":"Razooky","year":"2017","journal-title":"Genes"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7932","article-title":"Expression and functions of long noncoding RNAs during human T helper cell differentiation.","volume":"6","author":"Spurlock","year":"2015","journal-title":"Nat. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"595","DOI":"10.3892\/ol.2019.11182","article-title":"Research progress on the interactions between long non-coding RNAs and microRNAs in human cancer.","volume":"19","author":"Sun","year":"2020","journal-title":"Oncol. Lett."},{"key":"B27","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.bbrc.2020.04.117","article-title":"Chlamydia trachomatis plasmid-encoded protein pORF5 activates unfolded protein response to induce autophagy via MAPK\/ERK signaling pathway.","volume":"527","author":"Wen","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1038\/s41590-019-0542-7","article-title":"Inducible degradation of lncRNA Sros1 promotes IFN-gamma-mediated activation of innate immune responses by stabilizing Stat1 mRNA.","volume":"20","author":"Xu","year":"2019","journal-title":"Nat. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1080\/09168451.2018.1431518","article-title":"Silencing of lncRNA ZFAS1 inhibits malignancies by blocking Wnt\/beta-catenin signaling in gastric cancer cells.","volume":"82","author":"Xu","year":"2018","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41556-019-0311-8","article-title":"Cellular functions of long noncoding RNAs.","volume":"21","author":"Yao","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.1128\/jvi.75.6.2710-2728.2001","article-title":"Herpes simplex virus type 1 blocks the apoptotic host cell defense mechanisms that target Bcl-2 and manipulates activation of p38 mitogen-activated protein kinase to improve viral replication.","volume":"75","author":"Zachos","year":"2001","journal-title":"J. Virol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/sj.cr.7290257","article-title":"Activation and signaling of the p38 MAP kinase pathway.","volume":"15","author":"Zarubin","year":"2005","journal-title":"Cell Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.tim.2017.12.002","article-title":"Chlamydia Spreading from the Genital Tract to the Gastrointestinal Tract - A Two-Hit Hypothesis.","volume":"26","author":"Zhong","year":"2018","journal-title":"Trends Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1007\/s11427-013-4470-8","article-title":"PORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro-inflammatory cytokines via TLR2 activation in THP-1 cells.","volume":"56","author":"Zhou","year":"2013","journal-title":"Sci. China Life Sci."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"B36","first-page":"1633","article-title":"Identification of proteins interacting with pORF5 in the pathogenesis of C. trachomatis.","volume":"10","author":"Zou","year":"2018","journal-title":"Am. J. Transl. Res."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2020.593295\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T04:17:38Z","timestamp":1610252258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2020.593295\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":36,"alternative-id":["10.3389\/fmicb.2020.593295"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2020.593295","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]},"article-number":"593295"}}