{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:28:51Z","timestamp":1787887731856,"version":"build-2784847793"},"reference-count":89,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL135152 and P20GM103648"],"award-info":[{"award-number":["R01HL135152 and P20GM103648"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oklahoma Center for Adult Stem Cell Research","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"the Lundberg\u2010Kienlen Endowment fund","award":["to LL"],"award-info":[{"award-number":["to LL"]}]},{"name":"Veterans Affairs Merit Award","award":["2IO1BX000786-05A2"],"award-info":[{"award-number":["2IO1BX000786-05A2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and usually lethal lung disease and it has been widely accepted that fibroblast proliferation is one of the key characteristics of IPF. Long noncoding RNAs (lncRNAs) play vital roles in the pathogenesis of many diseases. In this study, we investigated the role of lncRNA FENDRR on fibroblast proliferation. Human lung fibroblasts stably overexpressing FENDRR showed a reduced cell proliferation compared to those expressing the control vector. On the other hand, FENDRR silencing increased fibroblast proliferation. FENDRR bound serine-arginine rich splicing factor 9 (SRSF9) and inhibited the phosphorylation of p70 ribosomal S6 kinase 1 (PS6K), a downstream protein of the mammalian target of rapamycin (mTOR) signaling. Silencing SRSF9 reduced fibroblast proliferation. FENDRR reduced \u03b2-catenin protein, but not mRNA levels. The reduction of \u03b2-catenin protein levels in lung fibroblasts by gene silencing or chemical inhibitor decreased fibroblast proliferation. Adenovirus-mediated FENDRR transfer to the lungs of mice reduced asbestos-induced fibrotic lesions and collagen deposition. RNA sequencing of lung tissues identified 7 cell proliferation-related genes that were up-regulated by asbestos but reversed by FENDRR. In conclusion, FENDRR inhibits fibroblast proliferation and functions as an anti-fibrotic lncRNA.<\/jats:p>","DOI":"10.3390\/ijms22168536","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T02:03:55Z","timestamp":1628474635000},"page":"8536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Long Noncoding RNA FENDRR Inhibits Lung Fibroblast Proliferation via a Reduction of \u03b2-Catenin"],"prefix":"10.3390","volume":"22","author":[{"given":"Lakmini Kumari","family":"Senavirathna","sequence":"first","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Liang","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Huang","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayan","family":"Bamunuarachchi","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao","family":"Xu","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanjin","family":"Dang","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pulavendran","family":"Sivasami","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-9064","authenticated-orcid":false,"given":"Kishore","family":"Vaddadi","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankha","family":"Hewawasam","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cheresh","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Department of Medicine, Division of Pulmonary & Critical Care Medicine, Jesse Brown VA Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Kamp","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Department of Medicine, Division of Pulmonary & Critical Care Medicine, Jesse Brown VA Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-4897","authenticated-orcid":false,"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA"},{"name":"Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1056\/NEJMra1705751","article-title":"Idiopathic Pulmonary Fibrosis","volume":"378","author":"Lederer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17074","DOI":"10.1038\/nrdp.2017.74","article-title":"Idiopathic pulmonary fibrosis","volume":"3","author":"Martinez","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","first-page":"1","article-title":"Idiopathic pulmonary fibrosis: An epithelial\/fibroblastic cross-talk disorder","volume":"3","author":"Selman","year":"2002","journal-title":"Respir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1164\/ajrccm.157.4.9707039","article-title":"Idiopathic Pulmonary Fibrosis","volume":"157","author":"Katzenstein","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1152\/physiolgenomics.00064.2015","article-title":"Interaction of long noncoding RNAs and microRNAs in the pathogenesis of idiopathic pulmonary fibrosis","volume":"47","author":"Huang","year":"2015","journal-title":"Physiol. Genom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.4161\/rna.26165","article-title":"The long non-coding RNA Fendrr links epigenetic control mechanisms to gene regulatory networks in mammalian embryogenesis","volume":"10","author":"Grote","year":"2013","journal-title":"RNA Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8639","DOI":"10.1038\/srep08639","article-title":"The lncRNA NRON modulates HIV-1 replication in a NFAT-dependent manner and is differentially regulated by early and late viral proteins","volume":"5","author":"Imam","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1080\/15476286.2019.1572448","article-title":"Long non-coding RNA PSMB8-AS1 regulates influenza virus replication","volume":"16","author":"More","year":"2019","journal-title":"RNA Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"646032","DOI":"10.3389\/fcell.2021.646032","article-title":"Long Non-coding RNAs and MicroRNAs Interplay in Osteogenic Differentiation of Mesenchymal Stem Cells","volume":"9","author":"Lanzillotti","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, X., Cheng, Z., Dai, L., Jiang, T., Jia, L., Jing, X., An, L., Wang, H., and Liu, M. (2019). Knockdown of Long Noncoding RNA H19 Represses the Progress of Pulmonary Fibrosis through the Transforming Growth Factor \u03b2\/Smad3 Pathway by Regulating MicroRNA 140. Mol. Cell. Biol., 39.","DOI":"10.1128\/MCB.00143-19"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1007\/s10753-018-0744-4","article-title":"The lncRNA H19 Mediates Pulmonary Fibrosis by Regulating the miR-196a\/COL1A1 Axis","volume":"41","author":"Lu","year":"2018","journal-title":"Inflammation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12931-020-01534-6","article-title":"Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis","volume":"21","author":"Wan","year":"2020","journal-title":"Respir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30921","DOI":"10.1038\/srep30921","article-title":"miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF","volume":"6","author":"Wu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.ymthe.2018.08.026","article-title":"lncITPF Promotes Pulmonary Fibrosis by Targeting hnRNP-L Depending on Its Host Gene ITGBL1","volume":"27","author":"Song","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1165\/rcmb.2018-0293OC","article-title":"Long Noncoding RNA FENDRR Exhibits Antifibrotic Activity in Pulmonary Fibrosis","volume":"62","author":"Huang","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13672","DOI":"10.1038\/s41598-020-70633-7","article-title":"Long non-coding RNA FENDRR regulates IFN\u03b3-induced M1 phenotype in macrophages","volume":"10","author":"Munteanu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S1440","DOI":"10.21037\/tcr.2016.12.46","article-title":"The role of long noncoding RNA FOXF1-AS1 as a tumor suppressor in non-small cell lung cancer","volume":"5","author":"Zheng","year":"2016","journal-title":"Transl. Cancer Res."},{"key":"ref_18","first-page":"1172","article-title":"The value of lncRNA FENDRR and FOXF1 as a prognostic factor for survival of lung adenocarcinoma","volume":"5","author":"Herrera","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","first-page":"103","article-title":"Downregulation of long noncoding RNA FENDRR predicts poor prognosis in renal cell carcinoma","volume":"17","author":"He","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.2147\/OTT.S195853","article-title":"LncRNA FENDRR attenuates colon cancer progression by repression of SOX4 protein","volume":"12","author":"Liu","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13045-014-0063-7","article-title":"Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression","volume":"7","author":"Xu","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Munteanu, M.C., Sethuraman, S.N., Singh, M.P., Malayer, J., and Ranjan, A. (2021). LncRNA FENDRR Expression Correlates with Tumor Immunogenicity. Genes, 12.","DOI":"10.3390\/genes12060897"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/emmm.201202218","article-title":"SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing \u03b2-catenin biosynthesis","volume":"5","author":"Fu","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1183\/09059180.00003613","article-title":"Common pathways in idiopathic pulmonary fibrosis and cancer","volume":"22","author":"Vancheri","year":"2013","journal-title":"Eur. Respir. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1165\/rcmb.2010-0113OC","article-title":"Nuclear \u03b2-catenin is increased in systemic sclerosis pulmonary fibrosis and promotes lung fibroblast migration and proliferation","volume":"45","author":"Lam","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14272","DOI":"10.1038\/s41598-017-14612-5","article-title":"Involvement of ER stress, PI3K\/AKT activation, and lung fibroblast proliferation in bleomycin-induced pulmonary fibrosis","volume":"7","author":"Hsu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1091\/mbc.e06-04-0320","article-title":"Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2","volume":"17","author":"Masckauchan","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2147\/OTT.S117933","article-title":"\u03b2-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma","volume":"10","author":"Yang","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sinnberg, T., Menzel, M., Ewerth, D., Sauer, B., Schwarz, M., Schaller, M., Garbe, C., and Schittek, B. (2011). \u03b2-Catenin signaling increases during melanoma progression and promotes tumor cell survival and chemoresistance. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023429"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1158\/1541-7786.MCR-14-0131","article-title":"Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer","volume":"12","author":"Das","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molcel.2008.03.013","article-title":"The Splicing Factor SF2\/ASF Regulates Translation Initiation by Enhancing Phosphorylation of 4E-BP1","volume":"30","author":"Michlewski","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1111\/j.1742-4658.2011.08274.x","article-title":"Shuttling SR proteins: More than splicing factors","volume":"278","author":"Twyffels","year":"2011","journal-title":"FEBS J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bbrc.2011.12.011","article-title":"Tumor suppressive microRNA-1 mediated novel apoptosis pathways through direct inhibition of splicing factor serine\/arginine-rich 9 (SRSF9\/SRp30c) in bladder cancer","volume":"417","author":"Yoshino","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7379","DOI":"10.1093\/nar\/gky615","article-title":"SRSF9 selectively represses ADAR2-mediated editing of brain-specific sites in primates","volume":"46","author":"Shanmugam","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nsmb1209","article-title":"The gene encoding the splicing factor SF2\/ASF is a proto-oncogene","volume":"14","author":"Karni","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Jiang, L., Huang, J., Higgs, B.W., Hu, Z., Xiao, Z., Yao, X., Conley, S., Zhong, H., Liu, Z., and Brohawn, P. (2016). Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005895"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1073\/pnas.96.9.4947","article-title":"T cell factor-activated transcription is not sufficient to induce anchorage-independent growth of epithelial cells expressing mutant beta-catenin","volume":"96","author":"Barth","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1183\/09031936.00185114","article-title":"Global incidence and mortality of idiopathic pulmonary fibrosis: A systematic review","volume":"46","author":"Hutchinson","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nrd.2017.170","article-title":"Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease","volume":"16","author":"Mora","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1165\/rcmb.2014-0445OC","article-title":"Novel Mechanisms for the Antifibrotic Action of Nintedanib","volume":"54","author":"Rangarajan","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1097\/BOR.0b013e32834b3309","article-title":"\u03b2-catenin signaling: A novel mediator of fibrosis and potential therapeutic target","volume":"23","author":"Lam","year":"2011","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"136","DOI":"10.7326\/0003-4819-134-2-200101160-00015","article-title":"Idiopathic pulmonary fibrosis: Prevailing and evolving hypotheses about its pathogenesis and implications for therapy","volume":"134","author":"Selman","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Navarro, C., Cano, C., Cuadros, M., Herrera-Merchan, A., Molina, M., and Blanco, A. (2016). A Mechanistic Study of lncRNA Fendrr Regulation of FoxF1 Lung Cancer Tumor Supressor, Springer International Publishing.","DOI":"10.1007\/978-3-319-31744-1_67"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"68339","DOI":"10.18632\/oncotarget.11630","article-title":"Loss of long noncoding RNA FOXF1-AS1 regulates epithelial-mesenchymal transition, stemness and metastasis of non-small cell lung cancer cells","volume":"7","author":"Miao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.7150\/ijbs.21722","article-title":"Antisense lncRNA FOXF1-AS1 Promotes Migration and Invasion of Osteosarcoma Cells Through the FOXF1\/MMP-2\/-9 Pathway","volume":"13","author":"Zhu","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1128\/MCB.01270-09","article-title":"Arginine methylation controls the subcellular localization and functions of the oncoprotein splicing factor SF2\/ASF","volume":"30","author":"Sinha","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1128\/MCB.22.19.6871-6882.2002","article-title":"Nuclear export and retention signals in the RS domain of SR proteins","volume":"22","author":"Cazalla","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1101\/gad.286404","article-title":"A novel role for shuttling SR proteins in mRNA translation","volume":"18","author":"Sanford","year":"2004","journal-title":"Genes Dev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15042","DOI":"10.1073\/pnas.0507827102","article-title":"Reversible phosphorylation differentially affects nuclear and cytoplasmic functions of splicing factor 2\/alternative splicing factor","volume":"102","author":"Sanford","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1242\/jcs.051011","article-title":"mTOR signaling at a glance","volume":"122","author":"Laplante","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"686984","DOI":"10.1155\/2014\/686984","article-title":"mTOR Signaling in Protein Translation Regulation: Implications in Cancer Genesis and Therapeutic Interventions","volume":"2014","author":"Showkat","year":"2014","journal-title":"Mol. Biol. Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/jmcb\/mjq038","article-title":"mTORC1 signaling: What we still don\u2019t know","volume":"3","author":"Wang","year":"2010","journal-title":"J. Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15323","DOI":"10.1073\/pnas.0801376105","article-title":"The splicing-factor oncoprotein SF2\/ASF activates mTORC1","volume":"105","author":"Karni","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/sj.onc.1204231","article-title":"Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: A comparative study with VEGF","volume":"20","author":"Zubilewicz","year":"2001","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lau, M.-T., So, W.-K., and Leung, P.C.K. (2013). Fibroblast growth factor 2 induces E-cadherin down-regulation via PI3K\/Akt\/mTOR and MAPK\/ERK signaling in ovarian cancer cells. PLoS ONE, 8.","DOI":"10.1371\/annotation\/ee15c511-4f60-4415-a0f4-c99dcf1bb2e2"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10456-005-5612-9","article-title":"Wnt\/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells","volume":"8","author":"Shawber","year":"2005","journal-title":"Angiogenesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7429","DOI":"10.1007\/s11033-020-05798-5","article-title":"Potential role of miR-214 in \u03b2-catenin gene expression within hepatocellular carcinoma","volume":"47","author":"Karimkhanloo","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.bbrc.2012.10.039","article-title":"MiR-214 inhibits cell growth in hepatocellular carcinoma through suppression of \u03b2-catenin","volume":"428","author":"Wang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Xia, H., Ooi, L.L.P.J., and Hui, K.M. (2012). MiR-214 Targets \u03b2-Catenin Pathway to Suppress Invasion, Stem-Like Traits and Recurrence of Human Hepatocellular Carcinoma. PLoS ONE, 7.","DOI":"10.1371\/annotation\/1be2a62e-45a1-4c13-9a8d-f265005a21e0"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1165\/rcmb.2013-0094TR","article-title":"Animal models of fibrotic lung disease","volume":"49","author":"Moore","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_62","first-page":"143","article-title":"Asbestos-induced lung diseases: An update","volume":"153","author":"Kamp","year":"2009","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1136\/thx.54.7.638","article-title":"The molecular basis of asbestos induced lung injury","volume":"54","author":"Kamp","year":"1999","journal-title":"Thorax"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1615\/JEnvironPatholToxicolOncol.v20.i2.30","article-title":"Increased TGF-beta1 in the lungs of asbestos-exposed rats and mice: Reduced expression in TNF-alpha receptor knockout mice","volume":"20","author":"Liu","year":"2001","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e14343","DOI":"10.14814\/phy2.14343","article-title":"Hypoxia and transforming growth factor \u03b21 regulation of long non-coding RNA transcriptomes in human pulmonary fibroblasts","volume":"8","author":"Senavirathna","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"R64","DOI":"10.1152\/ajpregu.2002.282.1.R64","article-title":"Activities of arginase I and II are limiting for endothelial cell proliferation","volume":"282","author":"Li","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-0436.1981.tb01123.x","article-title":"Role of polyamines in the control of cell proliferation and differentiation","volume":"19","author":"Heby","year":"1981","journal-title":"Differentiation"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1165\/rcmb.2006-0121OC","article-title":"Activation of alveolar macrophages via the alternative pathway in herpesvirus-induced lung fibrosis","volume":"35","author":"Mora","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/jmg.2004.027938","article-title":"Murine candidate bleomycin induced pulmonary fibrosis susceptibility genes identified by gene expression and sequence analysis of linkage regions","volume":"42","author":"Haston","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_70","first-page":"3034","article-title":"GPNMB silencing suppresses the proliferation and metastasis of osteosarcoma cells by blocking the PI3K\/Akt\/mTOR signaling pathway","volume":"39","author":"Jin","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.freeradbiomed.2006.11.031","article-title":"Nitric oxide in the pathogenesis of diffuse pulmonary fibrosis","volume":"42","author":"Hsu","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Geng, Y., Liu, X., Liang, J., Habiel, D.M., Kulur, V., Coelho, A.L., Deng, N., Xie, T., Wang, Y., and Liu, N. (2019). PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis. JCI Insight, 4.","DOI":"10.1172\/jci.insight.125326"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"eaar8356","DOI":"10.1126\/scitranslmed.aar8356","article-title":"PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-\u03b21 production","volume":"10","author":"Celada","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_74","first-page":"3207","article-title":"Scinderin-knockdown inhibits proliferation and promotes apoptosis in human breast carcinoma cells","volume":"16","author":"Jian","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3892\/ijo.2013.2170","article-title":"Suppression of SCIN inhibits human prostate cancer cell proliferation and induces G0\/G1 phase arrest","volume":"44","author":"Wang","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.gene.2014.10.013","article-title":"Lentivirus-mediated silencing of SCIN inhibits proliferation of human lung carcinoma cells","volume":"554","author":"Liu","year":"2015","journal-title":"Gene"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.gendis.2017.10.001","article-title":"Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice","volume":"4","author":"Peng","year":"2017","journal-title":"Genes Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev-pathol-012513-104706","article-title":"Pathogenesis of idiopathic pulmonary fibrosis","volume":"9","author":"Wolters","year":"2014","journal-title":"Annu. Rev. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1146\/annurev.cellbio.20.010403.113126","article-title":"The Wnt signaling pathway in development and disease","volume":"20","author":"Logan","year":"2004","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1165\/rcmb.2008-0485TR","article-title":"WNT signaling in lung disease: A failure or a regeneration signal?","volume":"42","author":"Eickelberg","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Selman, M., Pardo, A., and Kaminski, N. (2008). Idiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs?. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050062"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"16420","DOI":"10.1074\/jbc.M117.805747","article-title":"MicroRNA-101 attenuates pulmonary fibrosis by inhibiting fibroblast proliferation and activation","volume":"292","author":"Huang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1038\/s41598-018-21073-x","article-title":"Hypoxia induces pulmonary fibroblast proliferation through NFAT signaling","volume":"8","author":"Senavirathna","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/jgm.1080","article-title":"A novel approach for the construction of multiple shRNA expression vectors","volume":"9","author":"Gou","year":"2007","journal-title":"J. Gene Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1093\/nar\/gks1460","article-title":"miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt\/beta-catenin pathway","volume":"41","author":"Wang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e12915","DOI":"10.14814\/phy2.12915","article-title":"EZH2 enhances the differentiation of fibroblasts into myofibroblasts in idiopathic pulmonary fibrosis","volume":"4","author":"Xiao","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1165\/rcmb.2014-0038OC","article-title":"Asbestos-induced pulmonary fibrosis is augmented in 8-oxoguanine DNA glycosylase knockout mice","volume":"52","author":"Cheresh","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2144\/000112729","article-title":"Standardized quantification of pulmonary fibrosis in histological samples","volume":"44","author":"Gitter","year":"2008","journal-title":"Biotechniques"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:42:38Z","timestamp":1760164958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":89,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168536"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168536","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,9]]}}}