{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:10:11Z","timestamp":1789434611761,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic infection. The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases is poorly understood. In this study, we have shown that HCV exploits lncRNA long intergenic nonprotein\u2010coding RNA, p53 induced transcript (Linc\u2010Pint) in hepatocytes for enhancement of lipogenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We identified a lncRNA, Linc\u2010Pint, which is significantly down\u2010regulated in HCV\u2010replicating hepatocytes and liver specimens from HCV infected patients. Using RNA pull\u2010down proteomics, we identified serine\/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc\u2010Pint. A subsequent study demonstrated that overexpression of Linc\u2010Pint inhibits the expression of lipogenesis\u2010related genes, such as fatty acid synthase and ATP\u2010citrate lyase. We also observed that Linc\u2010Pint significantly inhibits HCV replication. Furthermore, HCV\u2010mediated enhanced lipogenesis can be controlled by exogenous Linc\u2010Pint expression. Together, our results suggested that\u00a0HCV\u2010mediated down\u2010regulation of Linc\u2010Pint enhances lipogenesis favoring virus replication and liver disease progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have shown that SRPK2 is a direct target of Linc\u2010Pint and that depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the role of Linc\u2010Pint in HCV\u2010associated liver pathogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31656","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T02:40:09Z","timestamp":1606272009000},"page":"41-54","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Inhibition of Long Noncoding RNA Linc\u2010Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis"],"prefix":"10.1097","volume":"74","author":[{"given":"Mousumi","family":"Khatun","sequence":"first","affiliation":[{"name":"Department of Pathology,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhayan","family":"Sur","sequence":"additional","affiliation":[{"name":"Department of Pathology,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Steele","sequence":"additional","affiliation":[{"name":"Department of Pathology,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna B.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathology,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,5,2]]},"reference":[{"key":"hep31656-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1038\/onc.2011.621","article-title":"Long non\u2010coding RNAs and cancer: A new frontier of translational research?","volume":"31","year":"2012","journal-title":"Oncogene"},{"key":"hep31656-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-biochem-051410-092902","article-title":"Genome regulation by long noncoding RNAs","volume":"81","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"hep31656-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ng.3192","article-title":"The landscape of long noncoding RNAs in the human transcriptome","volume":"47","year":"2015","journal-title":"Nat Genet"},{"key":"hep31656-bib-0004-20250824","first-page":"13","article-title":"Long non\u2010coding RNAs in multifactorial diseases: Another layer of complexity","volume":"4","year":"2018","journal-title":"Noncoding RNA"},{"key":"hep31656-bib-0005-20250824","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.tcb.2017.11.008","article-title":"Long noncoding RNA in cancer: Wiring signaling circuitry","volume":"28","year":"2018","journal-title":"Trends Cell Biol"},{"key":"hep31656-bib-0006-20250824","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ncrna.2018.03.001","article-title":"Exploring the mechanisms behind long noncoding RNAs and cancer","volume":"3","year":"2018","journal-title":"Noncoding RNA Res"},{"key":"hep31656-bib-0007-20250824","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3390\/v10110591","article-title":"Non\u2010coding RNAs and hepatitis C virus\u2010induced hepatocellular carcinoma","volume":"10","year":"2018","journal-title":"Viruses"},{"key":"hep31656-bib-0008-20250824","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3389\/fmicb.2017.01833","article-title":"Long non\u2010coding RNAs in hepatitis C virus\u2010infected cells","volume":"8","year":"2017","journal-title":"Front Microbiol"},{"key":"hep31656-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.15252\/embr.201541763","article-title":"Long noncoding RNA EGOT negatively affects the antiviral response and favors HCV replication","volume":"17","year":"2016","journal-title":"EMBO Rep"},{"key":"hep31656-bib-0010-20250824","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.virol.2016.02.020","article-title":"Long non\u2010coding RNA GAS5 inhibited hepatitis C virus replication by binding viral NS3 protein","volume":"492","year":"2016","journal-title":"Virology"},{"key":"hep31656-bib-0011-20250824","doi-asserted-by":"crossref","first-page":"10668","DOI":"10.1093\/nar\/gku713","article-title":"Negative regulation of the interferon response by an interferon\u2010induced long non\u2010coding RNA","volume":"42","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"hep31656-bib-0012-20250824","article-title":"Association between microRNA\u2010373 and long noncoding RNA NORAD in hepatitis C virus\u2010infected hepatocytes impairs Wee1 expression for growth promotion","volume":"92","year":"2018","journal-title":"J Virol"},{"key":"hep31656-bib-0013-20250824","article-title":"Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2","volume":"14","year":"2013","journal-title":"Genome Biol"},{"key":"hep31656-bib-0014-20250824","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1128\/JVI.80.9.4633-4639.2006","article-title":"Generation of infectious hepatitis C virus in immortalized human hepatocytes","volume":"80","year":"2006","journal-title":"J Virol"},{"key":"hep31656-bib-0015-20250824","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1128\/JVI.02383-15","article-title":"Knockdown of autophagy inhibits infectious hepatitis C virus release by the exosomal pathway","volume":"90","year":"2016","journal-title":"J Virol"},{"key":"hep31656-bib-0016-20250824","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/hep4.1362","article-title":"Repression of microRNA\u201030e by hepatitis C virus enhances fatty acid synthesis","volume":"3","year":"2019","journal-title":"Hepatol Commun"},{"key":"hep31656-bib-0017-20250824","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1128\/JVI.03085-14","article-title":"Hepatitis C virus\u2010mediated enhancement of microRNA miR\u2010373 impairs the JAK\/STAT signaling pathway","volume":"89","year":"2015","journal-title":"J Virol"},{"key":"hep31656-bib-0018-20250824","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13059-017-1331-y","article-title":"The human lncRNA LINC\u2010PINT inhibits tumor cell invasion through a highly conserved sequence element","volume":"18","year":"2017","journal-title":"Genome Biol"},{"key":"hep31656-bib-0019-20250824","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.cell.2017.10.037","article-title":"Post\u2010transcriptional regulation of de novo lipogenesis by mTORC1\u2010S6K1\u2010SRPK2 signaling","volume":"171","year":"2017","journal-title":"Cell"},{"key":"hep31656-bib-0020-20250824","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.gene.2016.03.051","article-title":"SRPK2 promotes the growth and migration of the colon cancer cells","volume":"586","year":"2016","journal-title":"Gene"},{"key":"hep31656-bib-0021-20250824","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.biopha.2018.03.079","article-title":"Enhanced expression of SRPK2 contributes to aggressive progression and metastasis in prostate cancer","volume":"102","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"hep31656-bib-0022-20250824","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00412-013-0407-z","article-title":"Regulation of splicing by SR proteins and SR protein\u2010specific kinases","volume":"122","year":"2013","journal-title":"Chromosoma"},{"key":"hep31656-bib-0023-20250824","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1083\/jcb.140.4.737","article-title":"SRPK2: A differentially expressed SR protein\u2010specific kinase involved in mediating the interaction and localization of pre\u2010mRNA splicing factors in mammalian cells","volume":"140","year":"1998","journal-title":"J Cell Biol"},{"key":"hep31656-bib-0024-20250824","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1128\/JVI.03327-13","article-title":"Forkhead box transcription factor regulation and lipid accumulation by hepatitis C virus","volume":"88","year":"2014","journal-title":"J Virol"},{"key":"hep31656-bib-0025-20250824","article-title":"Distinct roles for intracellular and extracellular lipids in hepatitis C virus infection","volume":"11","year":"2016","journal-title":"PLoS One"},{"key":"hep31656-bib-0026-20250824","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1074\/jbc.RA118.003392","article-title":"Distinct mechanisms govern the phosphorylation of different SR protein splicing factors","volume":"294","year":"2019","journal-title":"J Biol Chem"},{"key":"hep31656-bib-0027-20250824","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1128\/AAC.00113-10","article-title":"Inhibition of hepatitis C virus replication by a specific inhibitor of serine\u2010arginine\u2010rich protein kinase","volume":"54","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"hep31656-bib-0028-20250824","doi-asserted-by":"crossref","first-page":"9594","DOI":"10.1002\/jcb.28236","article-title":"Long noncoding RNA LINC\u2010PINT is inhibited in gastric cancer and predicts poor survival","volume":"120","year":"2019","journal-title":"J Cell Biochem"},{"key":"hep31656-bib-0029-20250824","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1080\/21691401.2019.1605371","article-title":"Long noncoding RNA LINC\u2010PINT inhibits non\u2010small cell lung cancer progression through sponging miR\u2010218\u20105p\/PDCD4","volume":"47","year":"2019","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"hep31656-bib-0030-20250824","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.2147\/OTT.S202938","article-title":"Long noncoding RNA LINC\u2010PINT promotes proliferation through EZH2 and predicts poor prognosis in clear cell renal cell carcinoma","volume":"12","year":"2019","journal-title":"Onco Targets Ther"},{"key":"hep31656-bib-0031-20250824","article-title":"Abnormal expression of the pre\u2010mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma","volume":"7","year":"2012","journal-title":"PLoS One"},{"key":"hep31656-bib-0032-20250824","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1158\/0008-5472.CAN-08-0021","article-title":"Serine\/arginine protein\u2010specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1","volume":"68","year":"2008","journal-title":"Cancer Res"},{"key":"hep31656-bib-0033-20250824","doi-asserted-by":"crossref","first-page":"11125","DOI":"10.1074\/jbc.274.16.11125","article-title":"The subcellular localization of SF2\/ASF is regulated by direct interaction with SR protein kinases (SRPKs)","volume":"274","year":"1999","journal-title":"J Biol Chem"},{"key":"hep31656-bib-0034-20250824","first-page":"778","article-title":"Lipid metabolism and carcinogenesis, cancer development","volume":"8","year":"2018","journal-title":"Am J Cancer Res"},{"key":"hep31656-bib-0035-20250824","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.cell.2012.04.031","article-title":"Insights into RNA biology from an atlas of mammalian mRNA\u2010binding proteins","volume":"149","year":"2012","journal-title":"Cell"},{"key":"hep31656-bib-0036-20250824","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.3892\/or.2017.5519","article-title":"MACC1 decreases the chemosensitivity of gastric cancer cells to oxaliplatin by regulating FASN expression","volume":"37","year":"2017","journal-title":"Oncol Rep"},{"key":"hep31656-bib-0037-20250824","article-title":"Fatty acid synthase regulates estrogen receptor\u2010alpha signaling in breast cancer cells","volume":"6","year":"2017","journal-title":"Oncogenesis"},{"key":"hep31656-bib-0038-20250824","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1080\/17460441.2016.1245286","article-title":"Recent advances in targeting the fatty acid biosynthetic pathway using fatty acid synthase inhibitors","volume":"11","year":"2016","journal-title":"Expert Opin Drug Discov"},{"key":"hep31656-bib-0039-20250824","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1080\/14728222.2017.1381087","article-title":"Fatty acid synthase (FASN) as a therapeutic target in breast cancer","volume":"21","year":"2017","journal-title":"Expert Opin Ther Targets"},{"key":"hep31656-bib-0040-20250824","doi-asserted-by":"crossref","first-page":"15669","DOI":"10.1073\/pnas.202608199","article-title":"Genomic analysis of the host response to hepatitis C virus infection","volume":"99","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep31656-bib-0041-20250824","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1073\/pnas.0409834102","article-title":"Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids","volume":"102","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep31656-bib-0042-20250824","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.jhep.2015.06.002","article-title":"Soraphen A: A broad\u2010spectrum antiviral natural product with potent anti\u2010hepatitis C virus activity","volume":"63","year":"2015","journal-title":"J Hepatol"},{"key":"hep31656-bib-0043-20250824","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ncb1631","article-title":"The lipid droplet is an important organelle for hepatitis C virus production","volume":"9","year":"2007","journal-title":"Nat Cell Biol"},{"key":"hep31656-bib-0044-20250824","doi-asserted-by":"crossref","first-page":"33466","DOI":"10.1074\/jbc.M109.019810","article-title":"Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice","volume":"284","year":"2009","journal-title":"J Biol Chem"},{"key":"hep31656-bib-0045-20250824","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/hep.25990","article-title":"Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to healthy humans","volume":"57","year":"2013","journal-title":"Hepatology"},{"key":"hep31656-bib-0046-20250824","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s12944-019-1136-y","article-title":"Hepatitis C virus nonstructural protein 5A perturbs lipid metabolism by modulating AMPK\/SREBP\u20101c signaling","volume":"18","year":"2019","journal-title":"Lipids Health Dis"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.31656","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.31656","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.31656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T23:02:23Z","timestamp":1756076543000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.31656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,2]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.31656","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,2]]},"assertion":[{"value":"2020-07-22","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-08","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}