{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:26:20Z","timestamp":1792106780311,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR29793\/PFN\/20\/1421\/2018"],"award-info":[{"award-number":["BT\/PR29793\/PFN\/20\/1421\/2018"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Sepsis is a dysregulated immune response disease affecting millions worldwide. Delayed diagnosis, poor prognosis, and disease heterogeneity make its treatment ineffective. miRNAs are imposingly involved in personalized medicine such as therapeutics, due to their high sensitivity and accuracy. Our study aimed to reveal the biomarkers that may be involved in the dysregulated immune response in sepsis and lung injury using a computational approach and in vivo validation studies. A sepsis miRNA Gene Expression Omnibus (GEO) dataset based on the former analysis of blood samples was used to identify differentially expressed miRNAs (DEMs) and associated hub genes. Sepsis-associated genes from the Comparative Toxicogenomics Database (CTD) that overlapped with identified DEM targets were utilized for network construction. In total, 317 genes were found to be regulated by 10 DEMs (three upregulated, namely miR-4634, miR-4638-5p, and miR-4769-5p, and seven downregulated, namely miR-4299, miR-451a, miR181a-2-3p, miR-16-5p, miR-5704, miR-144-3p, and miR-1290). Overall hub genes (HIP1, GJC1, MDM4, IL6R, and ERC1) and for miR-16-5p (SYNRG, TNRC6B, and LAMTOR3) were identified based on centrality measures (degree, betweenness, and closeness). In vivo validation of miRNAs in lung tissue showed significantly downregulated expression of miR-16-5p corroborating with our computational findings, whereas expression of miR-181a-2-3p and miR-451a were found to be upregulated in contrast to the computational approach. In conclusion, the differential expression pattern of miRNAs and hub genes reported in this study may help to unravel many unexplored regulatory pathways, leading to the identification of critical molecular targets for increased prognosis, diagnosis, and drug efficacy in sepsis and associated organ injuries.<\/jats:p>","DOI":"10.3390\/genes11111327","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T14:10:41Z","timestamp":1605017441000},"page":"1327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Identification and Validation of Potential miRNAs, as Biomarkers for Sepsis and Associated Lung Injury: A Network-Based Approach"],"prefix":"10.3390","volume":"11","author":[{"given":"Shaniya","family":"Ahmad","sequence":"first","affiliation":[{"name":"Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5695-0193","authenticated-orcid":false,"given":"Mohd Murshad","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. M. Z.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Center of Nanotechnology, King Abdulaziz University, Jeddah KSA.80216, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Sharma","sequence":"additional","affiliation":[{"name":"Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar L.","family":"Bilgrami","sequence":"additional","affiliation":[{"name":"Deanship of Scientific Research, King Abdulaziz University, Jeddah KSA.80216, Saudi Arabia"},{"name":"Department of Entomology, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Manda","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine and Applied Sciences, Defense Research Development, Organisation, New Delhi 110054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Ishrat","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7832","authenticated-orcid":false,"given":"Mansoor Ali","family":"Syed","sequence":"additional","affiliation":[{"name":"Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1586\/eri.12.50","article-title":"Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes","volume":"10","author":"Martin","year":"2012","journal-title":"Expert Rev. 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