{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:52:15Z","timestamp":1782222735284,"version":"3.54.5"},"update-to":[{"DOI":"10.12688\/f1000research.172407.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000}},{"DOI":"10.12688\/f1000research.172407.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000}}],"reference-count":40,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The authors received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>\n                    Background In this Bioinformatics study, we took in account the cell types variation of tumor microenvironment (TME) in Pancreatic Ductal Adenocarcinoma (PDAC), with a particular attention to miRNAs dysregulated pathways influencing immune responses, and especially memory CD4+ T cells. Methods For cell types and differentially expressed genes in memory CD4+ T cells, scRNA-seq was conducted on PDAC and non-tumoral pancreas samples. Putative miRNA targeting sequences on downregulated genes were investigated by three prediction databases, MiRWalk, TargetScan, and miRDB, and compared to GSE207345\u2019s differential expression with creation of Affymetrix Multispecies miRNA-4 Array. The miRNA\u2013mRNA interaction network was established in Cytoscape. Results Memory CD4+ T cells were significantly enriched in PDAC TME. At the same time, we observed genotype-specific repression of major immune and metabolic genes in these cells. Some miRNAs were significantly overexpressed in PDAC, and hsa-miR-1207-5p, hsa-miR-6805-5p, and hsa-miR-149-3p might target many immune-related or pancreatic enzyme-associated genes. Of these, a core of\n                    <ns5:italic>CLPS<\/ns5:italic>\n                    ,\n                    <ns5:italic>NR4A2<\/ns5:italic>\n                    , and\n                    <ns5:italic>SOCS3<\/ns5:italic>\n                    was most frequently targeted, which likely indicated the importance of these genes in immune evasion. Conclusions While memory CD4+ T cells exist within the PDAC TME, their activity is suppressed by miRNA-associated gene dysregulation. These data suggest candidate therapeutic approaches in which targeting of miRNAs could be used to normalize immune cells and promote anti-tumor immunity.\n                  <\/ns5:p>","DOI":"10.12688\/f1000research.172407.3","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:54:26Z","timestamp":1780476866000},"page":"1404","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioinformatics-based Investigation to Unveiling The miRNA-Immunity Axis in The Tumor Microenvironment of Pancreatic Cancer"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9175-1787","authenticated-orcid":false,"given":"Mohammed Salih","family":"AL-Janaby","sequence":"first","affiliation":[{"name":"Department of biotechnology, College of science Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0613-0493","authenticated-orcid":false,"given":"Salah H.","family":"Mannoush","sequence":"additional","affiliation":[{"name":"Department of biotechnology, College of science Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saif S.","family":"Al-Janabi","sequence":"additional","affiliation":[{"name":"Department of biotechnology, College of science Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-4483","authenticated-orcid":false,"given":"Ahmed AbdulJabbar","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Department of biotechnology, College of science Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Hazim","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"Department of biotechnology, College of science Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anmar Kamil","family":"Alalwani","sequence":"additional","affiliation":[{"name":"Department of biotechnology, College of science Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7769-0989","authenticated-orcid":false,"given":"Mustafa M.","family":"Fahad","sequence":"additional","affiliation":[{"name":"Center of Desert Studies Al-Anbar Al_Ramadi 31001 University of Anbar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4686-4695","DOI":"10.1038\/s41388-022-02448-x","article-title":"The roles of intratumour heterogeneity in the biology and treatment of pancreatic ductal adenocarcinoma.","volume":"41","author":"T Evan","year":"2022","journal-title":"Oncogene."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/s41467-024-45097-2","article-title":"Reconstitution of human PDAC using primary cells reveals oncogenic transcriptomic features at tumor onset.","volume":"15","author":"Y Xu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"184-196","DOI":"10.1016\/j.semcancer.2021.03.006","article-title":"Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment.","volume":"82","author":"L Boyd","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"18020-18031","DOI":"10.1002\/cam4.6407","article-title":"Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single-cell analysis.","volume":"12","author":"S Byeon","year":"2023","journal-title":"Cancer Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"7956-7968","DOI":"10.3748\/wjg.v27.i46.7956","article-title":"T cells in pancreatic cancer stroma.","volume":"27","author":"M Goulart","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"489-492","DOI":"10.22159\/ajpcr.2018.v11i6.25881","article-title":"RELATIONSHIP BETWEEN SOME IMMUNOLOGICAL FACTORS AND TYPE 2 DIABETES MELLITUS IN IRAQI PATIENTS.","volume":"11","author":"M Al-Janaby","year":"2018","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"725-740","DOI":"10.1007\/s10555-023-10127-w","article-title":"Targeting miRNA and using miRNA as potential therapeutic options to bypass resistance in pancreatic ductal adenocarcinoma.","volume":"42","author":"M Vahabi","year":"2023","journal-title":"Cancer Metastasis Rev."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"356-362","DOI":"10.4103\/bbrj.bbrj_246_24","article-title":"Molecular detection of Chlamydia pneumoniae, Haemophilus influenza, and Streptococcus pneumoniae and expression of miR-146, miR-16, and miR-221 in patients with chronic obstructive pulmonary diseases.","volume":"8","author":"N Husseini","year":"2024","journal-title":"Biomedical and Biotechnology Research Journal."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"163-186","DOI":"10.1007\/s10585-023-10256-0","article-title":"miRNAs in pancreatic cancer progression and metastasis.","volume":"41","author":"E Mok","year":"2024","journal-title":"Clin. Exp. Metastasis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3703","DOI":"10.3390\/cancers12123703","article-title":"The emerging role of miRNAs for the radiation treatment of pancreatic cancer.","volume":"12","author":"L Nguyen","year":"2020","journal-title":"Cancers (Basel)."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.3390\/cancers12082274","article-title":"Mechanisms of T-cell exhaustion in pancreatic cancer.","volume":"12","author":"D Saka","year":"2020","journal-title":"Cancers (Basel)."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"58-70","DOI":"10.1016\/j.ajpath.2018.10.005","article-title":"miRNA and gene expression in pancreatic ductal adenocarcinoma.","volume":"189","author":"A Tesfaye","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.3390\/genes13101868","article-title":"The emerging role of microRNAs and autophagy mechanism in pancreatic cancer progression: future therapeutic approaches.","volume":"13","author":"E Koustas","year":"2022","journal-title":"Genes (Basel)."},{"key":"ref14","first-page":"13","article-title":"Investigating the Impact of miR-21 rs1292037: T > C, miR-449b rs10061133: A > G and PDCD4 rs6585018: G > A Haplotype Polymorphism in Iraqi Breast Cancer Patients.","volume":"4","author":"M Al-janaby","year":"2021","journal-title":"Medical Journal of Babylon."},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-025-00506-0","article-title":"A Single-Cell Network Approach to Decode Metabolic Regulation in Gynecologic and Breast Cancers.","author":"A Srivastava","year":"2024"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"btae426","DOI":"10.1093\/bioinformatics\/btae426","article-title":"ScType enables fast and accurate cell type identification from spatial transcriptomics data.","volume":"40","author":"K Nader","year":"2024","journal-title":"Bioinformatics."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"15-18","DOI":"10.1186\/s12967-020-02689-y","article-title":"Three hematologic\/immune system-specific expressed genes are considered as the potential biomarkers for the diagnosis of early rheumatoid arthritis through bioinformatics analysis.","volume":"19","author":"Q Cheng","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0206239","DOI":"10.1371\/journal.pone.0206239","article-title":"miRWalk: an online resource for prediction of microRNA binding sites.","volume":"13","author":"C Sticht","year":"2018","journal-title":"PLoS One."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.3390\/biomedicines12081713","article-title":"Using microRNAs Networks to Understand Pancreatic Cancer\u2014A Literature Review.","volume":"12","author":"O Przybyszewski","year":"2024","journal-title":"Biomedicine."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"163-169","DOI":"10.4103\/bbrj.bbrj_46_23","article-title":"In Silico Functional Network Analysis for the Identification of Novel Target Associated with SCN1A Gene.","volume":"7","author":"A Khatri","year":"2023","journal-title":"Biomedical and Biotechnology Research Journal."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e31346","DOI":"10.1016\/j.heliyon.2024.e31346","article-title":"Pancreatic cancer cells hijack tumor suppressive microRNA-26a to promote radioresistance and potentiate tumor repopulation.","volume":"10","author":"M Jiang","year":"2024","journal-title":"Heliyon."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"4359-4372","DOI":"10.1158\/0008-5472.CAN-22-1190","article-title":"Quantitative spatial profiling of immune populations in pancreatic ductal adenocarcinoma reveals tumor microenvironment heterogeneity and prognostic biomarkers.","volume":"82","author":"H Mi","year":"2022","journal-title":"Cancer Res."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.21037\/apc.2019.06.03","article-title":"Ductal vs. acinar? Recent insights into identifying cell lineage of pancreatic ductal adenocarcinoma.","volume":"2","author":"Y Xu","year":"2019","journal-title":"Annals of Pancreatic Cancer."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"293-300","DOI":"10.1038\/s41586-019-1805-z","article-title":"c-Jun overexpression in CAR T cells induces exhaustion resistance.","volume":"576","author":"R Lynn","year":"2019","journal-title":"Nature."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"159-163","DOI":"10.4103\/bbrj.bbrj_248_21","article-title":"Molecular facets and biochemical cross-talk of angiogenesis: Potential therapeutic targets.","volume":"6","author":"J Yodhaanjali","year":"2022","journal-title":"Biomedical and Biotechnology Research Journal."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e2106083119","DOI":"10.1073\/pnas.2106083119","article-title":"MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection.","volume":"119","author":"E Stelekati","year":"2022","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e008628","DOI":"10.1136\/jitc-2023-008628","article-title":"Dysregulation of CD4+ and CD8+ resident memory T, myeloid, and stromal cells in steroid-experienced, checkpoint inhibitor colitis.","volume":"12","author":"J He","year":"2024","journal-title":"J. Immunother. Cancer."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"881801","DOI":"10.3389\/fonc.2022.881801","article-title":"SOCS3 acts as an onco-immunological biomarker with value in assessing the tumor microenvironment, pathological staging, histological subtypes, therapeutic effect, and prognoses of several types of cancer.","volume":"12","author":"L Dai","year":"2022","journal-title":"Front. Oncol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.3389\/fimmu.2020.02168","article-title":"CXCR4 inhibition counteracts immunosuppressive properties of metastatic NSCLC stem cells.","volume":"11","author":"O Fortunato","year":"2020","journal-title":"Front. Immunol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"102453","DOI":"10.1016\/j.jaut.2020.102453","article-title":"The pivotal role of CD69 in autoimmunity.","volume":"111","author":"A Gorabi","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1-14","DOI":"10.2147\/ITT.S439969","article-title":"CD69 is a promising immunotherapy and prognosis prediction target in cancer.","volume":"13","author":"Y Li","year":"2024","journal-title":"ImmunoTargets and Therapy."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"517-523","DOI":"10.4103\/bbrj.bbrj_349_24","article-title":"Sarcoidosis and Non-Small Cell Lung Cancer: Expression of miR-145, miR-301, and miR-449.","volume":"8","author":"N Khosravi","year":"2024","journal-title":"Biomedical and Biotechnology Research Journal."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"12848","DOI":"10.3390\/ijms252312848","article-title":"Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.","volume":"25","author":"O Franzese","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1-15","DOI":"10.1155\/2022\/5006123","article-title":"miR-149-3p Is a Potential Prognosis Biomarker and Correlated with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma.","volume":"2022","author":"X Lu","year":"2022","journal-title":"Int. J. Endocrinol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"190061","DOI":"10.1098\/rsob.190061","article-title":"miR-149-3p reverses CD8+ T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells.","volume":"9","author":"M Zhang","year":"2019","journal-title":"Open Biol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"946-953","DOI":"10.1002\/eji.201646837","article-title":"CD69: from activation marker to metabolic gatekeeper.","volume":"47","author":"D Cibri\u00e1n","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"374-379","DOI":"10.4103\/bbrj.bbrj_182_21","article-title":"Co-regulatory network of transcription factor and microRNA: A key player of gene regulation.","volume":"5","author":"A Pande","year":"2021","journal-title":"Biomedical and Biotechnology Research Journal."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"13626","DOI":"10.1038\/s41598-021-92720-z","article-title":"High expression of DNA damage-inducible transcript 4 (DDIT4) is associated with advanced pathological features in the patients with colorectal cancer.","volume":"11","author":"F Fattahi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"19403","DOI":"10.1038\/s41598-023-46484-3","article-title":"Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors.","volume":"13","author":"F Tajik","year":"2023","journal-title":"Sci. Rep."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"90-94","DOI":"10.4103\/bbrj.bbrj_5_20","article-title":"Review on role of CD4 T-cells in patients with respiratory illness and human immunodeficiency virus infection.","volume":"4","author":"P Gaur","year":"2020","journal-title":"Biomedical and Biotechnology Research Journal."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:24:08Z","timestamp":1782221048000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":40,"URL":"https:\/\/doi.org\/10.12688\/f1000research.172407.3","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.172407.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.172407.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.200514.r488347","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.200514.r487578","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.200514.r487577","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.200514.r488347","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.200514.r487578","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.200514.r487578, Fadehl Lafta, Department of Biology, College of Science, University of Baghdad, Baghdad, Baghdad Governorate, 23 Jun 2026, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3#referee-response-487578","order":0,"name":"referee-response-487578","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.200514.r487577, J\u00f6rg Kleeff, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, Halle, 03 Jun 2026, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3#referee-response-487577","order":1,"name":"referee-response-487577","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.200514.r488347, Mahmoud Hamid Al-Fahdawi, Al-Nahrain University, Baghdad, 23 Jun 2026, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1404\/v3#referee-response-488347","order":2,"name":"referee-response-488347","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}