{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:19:16Z","timestamp":1778131156270,"version":"3.51.4"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","award":["13854"],"award-info":[{"award-number":["13854"]}],"id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3\u2019UTR (3\u2019UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, particularly in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells affect 3\u2019UTR-APA and IPA in primary human macrophages was unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we isolated primary human monocytes from healthy donors, differentiated and polarized them into a pro-inflammatory state and performed indirect co-cultures with CRC cells. ChrRNA-Seq and 3\u2019RNA-Seq was performed to quantify gene expression and characterize new 3\u2019UTR-APA and IPA mRNA isoforms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results show that polarization of human macrophages from na\u00efve to a pro-inflammatory state causes a marked increase of proximal polyA site selection in the 3\u2019UTR and IPA events in genes relevant to macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3\u2019UTR-APA and IPA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro-tumoral genes and induces 3\u2019UTR-APA alterations. Notably, some of these gene expression differences were also found in tumor-associated macrophages of CRC patients, indicating that they are physiologically relevant. Upon macrophage pro-inflammatory polarization,\n                      <jats:italic>SRSF12<\/jats:italic>\n                      is the pre-mRNA processing gene that is most upregulated. After\n                      <jats:italic>SRSF12<\/jats:italic>\n                      knockdown in M1 macrophages there is a global downregulation of gene expression, in particular in genes involved in gene expression regulation and in immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our results reveal new 3\u2019UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools. Furthermore, our results highlight a function for\n                      <jats:italic>SRSF12<\/jats:italic>\n                      in pro-inflammatory macrophages, key cells in the tumor response.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1182525","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T11:54:50Z","timestamp":1686225290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages"],"prefix":"10.3389","volume":"14","author":[{"given":"Joana","family":"Wilton","sequence":"first","affiliation":[]},{"given":"Filipa Lopes","family":"de Mendon\u00e7a","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Pereira-Castro","sequence":"additional","affiliation":[]},{"given":"Michael","family":"Tellier","sequence":"additional","affiliation":[]},{"given":"Takayuki","family":"Nojima","sequence":"additional","affiliation":[]},{"given":"Angela M.","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Jaime","family":"Freitas","sequence":"additional","affiliation":[]},{"given":"Shona","family":"Murphy","sequence":"additional","affiliation":[]},{"given":"Maria Jose","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Nicholas J.","family":"Proudfoot","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Moreira","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01875","article-title":"The two faces of tumour-associated macrophages and their clinical significance in colorectal cancer","volume":"10","author":"Pinto","year":"2019","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.300168","article-title":"tumour-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization lessons and open questions","volume":"33","author":"Mantovani","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417028-5.00006-5","article-title":"Macrophage activation and polarization as an adaptive component of innate immunity","volume":"120","author":"Locati","year":"2013","journal-title":"Adv Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8260","article-title":"Adenosine augments IL-10 production by macrophages through an a 2B receptor-mediated posttranscriptional mechanism","volume":"175","author":"N\u00e9meth","year":"2005","journal-title":"J Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2009.02.008","article-title":"tumour-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation","volume":"70","author":"Mantovani","year":"2009","journal-title":"Hum Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.741305","article-title":"tumour-associated macrophages and their functional transformation in the hypoxic tumour microenvironment","volume":"12","author":"He","year":"2021","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nri3088","article-title":"Transcriptional regulation of macrophage polarization: enabling diversity with identity","volume":"11","author":"Lawrence","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2013.03.005","article-title":"Alternative cleavage and polyadenylation: the long and short of it","volume":"38","author":"Tian","year":"2013","journal-title":"Trends Biochem Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2017.03.002","article-title":"Expression of Rac1 alternative 3\u2032 UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons","volume":"1860","author":"Braz","year":"2017","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature14321","article-title":"Alternative 3\u2019 UTRs act as scaffolds to regulate membrane protein localization","volume":"522","author":"Berkovits","year":"2015","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pgen.1006338","article-title":"Widespread shortening of 3\u2019 untranslated regions and increased exon inclusion are evolutionarily conserved features of innate immune responses to infection","volume":"12","author":"Pai","year":"2016","journal-title":"PloS Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.80.2.451","article-title":"Quantitative conservation of chromatin-bound RNA polymerases I and II in mitosis","volume":"80","author":"Matsui","year":"1979","journal-title":"Implications Chromosome Struct J Cell Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120116-024704","article-title":"Regulation by 3\u2032\u2013untranslated regions","volume":"51","author":"Mayr","year":"2017","journal-title":"Annu Rev Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.031","article-title":"Insights into RNA biology from an atlas of mammalian mRNA-binding proteins","volume":"149","author":"Castello","year":"2012","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/nrg3482","article-title":"Alternative cleavage and polyadenylation: extent, regulation and function","volume":"14","author":"Elkon","year":"2013","journal-title":"Nat Rev Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nrm.2016.116","article-title":"Alternative polyadenylation of mRNA precursors","volume":"18","author":"Tian","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/gr.132563.111","article-title":"A quantitative atlas of polyadenylation in five mammals","volume":"22","author":"Derti","year":"2012","journal-title":"Genome Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1261\/rna.035899.112","article-title":"Alternative polyadenylation: new insights from global analyses","volume":"18","author":"Shi","year":"2012","journal-title":"RNA"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki158","article-title":"A large-scale analysis of mRNA polyadenylation of human and mouse genes","volume":"33","author":"Tian","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1016\/j.cell.2018.10.007","article-title":"A membraneless organelle associated with the endoplasmic reticulum enables 3\u2032UTR-mediated protein-protein interactions","volume":"175","author":"Ma","year":"2018","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/wrna.1653","article-title":"On the function and relevance of alternative 3\u2032-UTRs in gene expression regulation","author":"Pereira-Castro","year":"2021","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1101\/gr.5532707","article-title":"Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing","volume":"17","author":"Tian","year":"2007","journal-title":"Genome Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-04112-z","article-title":"Widespread intronic polyadenylation diversifies immune cell transcriptomes","volume":"9","author":"Singh","year":"2018","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0465-8","article-title":"Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia","volume":"561","author":"Lee","year":"2018","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2766","DOI":"10.1016\/j.celrep.2019.02.049","article-title":"Regulation of intronic polyadenylation by PCF11 impacts mRNA expression of long genes","volume":"26","author":"Wang","year":"2019","journal-title":"Cell Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155390","article-title":"Sharp p a, burge CB. proliferating cells express mRNAs with shortened 3\u2019 UTRs and fewer microRNA target sites","volume":"320","author":"Sandberg","year":"2008","journal-title":"Sci (1979)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.016","article-title":"Widespread shortening of 3\u2019UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells","volume":"138","author":"Mayr","year":"2009","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"14605","DOI":"10.1038\/ncomms14605","article-title":"The role of alternative polyadenylation in the antiviral innate immune response","volume":"8","author":"Jia","year":"2017","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2017.04.023","article-title":"Neutral PEGylated liposomal formulation for efficient folate-mediated delivery of MCL1 siRNA to activated macrophages","volume":"155","author":"Nogueira","year":"2017","journal-title":"Colloids Surf B Biointerfaces."},{"key":"B32","article-title":"Simultaneous studies of gene expression and alternative polyadenylation in primary human immune cells, Chap 16, in Methods Enzymol, mRNA 3' End Processing and Metabolism","author":"Wilton","year":""},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2015.39","article-title":"Differentiation of human monocytes and derived subsets of macrophages and dendritic cells by the HLDA10 monoclonal antibody panel","volume":"5","author":"Ohradanova-Repic","year":"2016","journal-title":"Clin Transl Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.012","article-title":"Mammalian NET-seq analysis defines nascent RNA profiles and associated RNA processing genome-wide","volume":"11","author":"Nojima","year":"2016","journal-title":"Nat Protoc"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7303","article-title":"Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression","volume":"177","author":"Martinez","year":"2006","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0160891","article-title":"Intricate macrophage-colorectal cancer cell communication in response to radiation","volume":"11","author":"Pinto","year":"2016","journal-title":"PloS One"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.566511","article-title":"tumour-associated macrophages in human breast, colorectal, lung, ovarian and prostate cancers","volume":"10","author":"Larionova","year":"2020","journal-title":"Front Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2013.35","article-title":"Epigenetic and genetic features of 24 colon cancer cell lines","volume":"2","author":"Ahmed","year":"2013","journal-title":"Oncogenesis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aah5509","article-title":"tumour-derived exosomes modulate PD-L1 expression in monocytes","volume":"2","author":"Haderk","year":"2017","journal-title":"Sci Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14049","article-title":"The role of exosomes on colorectal cancer: a review","volume":"33","author":"Ruiz-L\u00f3pez","year":"2018","journal-title":"J Gastroenterol Hepatol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21176009","article-title":"Roles of il-1 in cancer: from tumour progression to resistance to targeted therapies","volume":"21","author":"Gelfo","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.247","article-title":"Macrophage-derived IL-1B stimulates wnt signaling and growth of colon cancer cells: a crosstalk interrupted by vitamin D\"3","volume":"28","author":"Kaler","year":"2009","journal-title":"Oncogene"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12931-019-1176-x","article-title":"Wnt signaling regulates trans-differentiation of stem cell like type 2 alveolar epithelial cells to type 1 epithelial cells","volume":"20","author":"Abdelwahab","year":"2019","journal-title":"Respir Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-21601-9","article-title":"Understanding the functional role of genistein in the bone differentiation in mouse osteoblastic cell line MC3T3-E1 by RNA-seq analysis","volume":"8","author":"Kim","year":"2018","journal-title":"Sci Rep"},{"key":"B45","doi-asserted-by":"publisher","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":"B46","doi-asserted-by":"publisher","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":"Masckauch\u00e1n","year":"2005","journal-title":"Angiogenesis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01341","article-title":"Emerging roles of wnt ligands in human colorectal cancer","volume":"10","author":"Nie","year":"2020","journal-title":"Front Oncol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa266","article-title":"APAlyzer: a bioinformatics package for analysis of alternative polyadenylation isoforms","volume":"36","author":"Wang","year":"2020","journal-title":"Bioinformatics"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085461","article-title":"Interleukin 17 receptor a modulates monocyte subsets and macrophage generation in vivo","volume":"9","author":"Ge","year":"2014","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32122","article-title":"IL-17R deletion predicts high-grade colorectal cancer and poor clinical outcomes","volume":"145","author":"Yan","year":"2019","journal-title":"Int J Cancer."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0628","article-title":"Targeting prpk function blocks colon cancer metastasis","volume":"17","author":"Zykova","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2574","article-title":"Active wnt proteins are secreted on exosomes","volume":"14","author":"Gross","year":"2012","journal-title":"Nat Cell Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx597","article-title":"ALYREF mainly binds to the 5\u2032 and the 3\u2032 regions of the mRNA in vivo","volume":"45","author":"Shi","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.29630","article-title":"IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs","volume":"6","author":"Zhou","year":"2017","journal-title":"Elife"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2194910","article-title":"Transcriptome and targetome analysis in MIR155 expressing cells using RNA-seq","volume":"16","author":"Xu","year":"2010","journal-title":"Rna"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.05.003","article-title":"TPL2 expression is correlated with distant metastasis and poor prognosis in colorectal cancer","volume":"79","author":"Pyo","year":"2018","journal-title":"Hum Pathol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1101\/gad.250993.114","article-title":"CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3\u2032 processing","volume":"28","author":"Chan","year":"2014","journal-title":"Genes Dev"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.21873\/cgp.20028","article-title":"Mining exosomal genes for pancreatic cancer targets","volume":"14","author":"Makler","year":"2017","journal-title":"Cancer Genomics Proteomics."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0254","article-title":"A peculiar molecular profile of umbilical cord-mesenchymal stromal cells drives their inhibitory effects on multiple myeloma cell growth and tumour progression","volume":"24","author":"Ciavarella","year":"2015","journal-title":"Stem Cells Dev"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.709931","article-title":"Exploration of a novel prognostic risk signature and its effect on the immune response in nasopharyngeal carcinoma","volume":"11","author":"Zhao","year":"2021","journal-title":"Front Oncol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.8609","article-title":"Pre-b cell leukemia transcription factor 3 induces inflammatory responses in human umbilical vein endothelial cells and murine sepsis via acting a competing endogenous RNA for high mobility group box 1 protein","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol Med Rep"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17196","article-title":"The regulation of PBXs and their emerging role in cancer","volume":"26","author":"Liu","year":"2022","journal-title":"J Cell Mol Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i48.18260","article-title":"PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK\/ERK signaling pathway","volume":"20","author":"Han","year":"2014","journal-title":"World J Gastroenterol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4161\/onci.28270","article-title":"The role of CUX1 in antagonizing NF-\u03baB signaling in TAMs","volume":"3","author":"K\u00fchnemuth","year":"2014","journal-title":"Oncoimmunology"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/\u03b2-Catenin Signaling in Development and Disease","volume":"129","author":"Clevers","year":"2019","journal-title":"Cells"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41413-018-0023-x","article-title":"Oxidized phospholipids are ligands for LRP6","volume":"6","author":"Wang","year":"2018","journal-title":"Bone Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.07.017","article-title":"Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance","volume":"9","author":"Hamdollah Zadeh","year":"2015","journal-title":"Mol Oncol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200112)44:12<2879::AID-ART476>3.0.CO;2-4","article-title":"TIA-1 regulates the production of tumour necrosis factor alpha in macrophages, but not in lymphocytes","volume":"44","author":"Saito","year":"2001","journal-title":"Arthritis Rheumatol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00646","article-title":"Understanding metal dynamics between cancer cells and macrophages: competition or synergism","volume":"10","author":"Serra","year":"2020","journal-title":"Front Oncol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057034","article-title":"Rab6a\/a\u2019 are important golgi regulators of pro-inflammatory TNF secretion in macrophages","volume":"8","author":"Micaroni","year":"2013","journal-title":"PloS One"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/3241351","article-title":"Na+\/H+-exchanger family as novel prognostic biomarkers in colorectal cancer","volume":"2021","author":"Zhou","year":"2021","journal-title":"J Oncol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103967200","article-title":"Serine-arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing","volume":"276","author":"Cowper","year":"2001","journal-title":"J Biol Chem"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600300","article-title":"Muscleblind proteins regulate alternative splicing","volume":"23","author":"Ho","year":"2004","journal-title":"EMBO J"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.02","article-title":"Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease","volume":"157","author":"Batra","year":"2015","journal-title":"Mol Cell"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.5.1147","article-title":"A role for Cdc42 in macrophage chemotaxis","volume":"141","author":"Allen","year":"1998","journal-title":"J Cell Biol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.1.141","article-title":"Rac1 and Cdc42 are required for phagocytosis, but not NF-\u03baB-dependent gene expression, in macrophages challenged with pseudomonas aeruginosa","volume":"275","author":"Lee","year":"2000","journal-title":"J Biol Chem"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.01.003","article-title":"Tumour-associated macrophages are a distinct M2 polarized population promoting tumour progression: potential targets of anti-cancer therapy","volume":"42","author":"Sica","year":"2006","journal-title":"Eur J Cancer."},{"key":"B78","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s00262-020-02669-7","article-title":"Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels tumour heterogeneity plus M2-like tumour-associated macrophage infiltration and aggressiveness in TNBC","volume":"70","author":"Bao","year":"2021","journal-title":"Cancer Immunol Immunother."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep11874","article-title":"IL-17A and its homologs IL-25\/IL-17E recruit the c-RAF\/S6 kinase pathway and the generation of pro-oncogenic LMW-e in breast cancer cells","volume":"5","author":"Mombelli","year":"2015","journal-title":"Sci Rep"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00770-1","article-title":"Functional homology between yeast piD261\/Bud32 and human PRPK: both phosphorylate p53 and PRPK partially complements piD261\/Bud32 deficiency","volume":"549","author":"Facchin","year":"2003","journal-title":"FEBS Lett"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0543","article-title":"Alternative cleavage and polyadenylation during colorectal cancer development","volume":"18","author":"Morris","year":"2012","journal-title":"Clin Cancer Res"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)82000-0","article-title":"The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during b cell differentiation","volume":"87","author":"Takagaki","year":"1996","journal-title":"Cell"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.4.10.2151-2160.1984","article-title":"Calcitonin\/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites","volume":"4","author":"Amara","year":"1984","journal-title":"Mol Cell Biol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.13.2547","article-title":"Alternative poly(A) site selection in complex transcription units: means to an end","volume":"25","author":"Edwalds-Gilbert","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"B85","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cell.2012.05.029","article-title":"U1 snRNP determines mRNA length and regulates isoform expression","volume":"150","author":"Berg","year":"2012","journal-title":"Cell"},{"key":"B86","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1002\/wrna.1260","article-title":"The RNAissance family: SR proteins as multifaceted regulators of gene expression","volume":"6","author":"Howard","year":"2015","journal-title":"Wiley Interdiscip Rev RNA."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-seq","volume":"25","author":"Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"B88","article-title":"Mapping RNA-seq reads with STAR","volume":"51","author":"Dobin","year":"2016","journal-title":"Curr Protoc Bioinf"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1114s51","article-title":"Mapping RNA-seq Reads with STAR","volume":"51","author":"Dobin","year":"2015","journal-title":"Curr Protoc Bioinformatics"},{"key":"B90","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz461","article-title":"hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles","volume":"47","author":"Fischl","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00018-022-04172-x","article-title":"MCL1 alternative polyadenylation is essential for cell survival and mitochondria morphology","volume":"79","author":"Pereira-Castro","year":"2022","journal-title":"Cell Mol Life Sci"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.027","article-title":"Mammalian NET-seq reveals genome-wide nascent transcription coupled to RNA processing","volume":"161","author":"Nojima","year":"2015","journal-title":"Cell"},{"key":"B96","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B98","unstructured":"The cancer genome atlas"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1182525\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T11:54:56Z","timestamp":1686225296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1182525\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,8]]},"references-count":98,"alternative-id":["10.3389\/fimmu.2023.1182525"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1182525","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.02.24.529734","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,8]]},"article-number":"1182525"}}