{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:17:15Z","timestamp":1787066235146,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2023R1A2C1007756"],"award-info":[{"award-number":["2023R1A2C1007756"]}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2023R1A2C1007756"],"award-info":[{"award-number":["2023R1A2C1007756"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hankuk University of Foreign","award":["2023R1A2C1007756"],"award-info":[{"award-number":["2023R1A2C1007756"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The human body is a complex network of systems that is harmonized with multiple biological components. To understand these interactions is very challenging. With rapid development of advanced sequencing technologies, massive amounts of data such as mRNA, miRNA are rapidly accumulated. The integrated analysis of mRNA\u2013miRNA has brought an extensive understanding of complex biological systems and pathological mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs that intricately regulate target gene products, resulting in the inhibition of gene expression. While these miRNAs play crucial roles in essential biological processes\u2014ranging from immunity and metabolism to cell death\u2014their specific impacts on diseases remain unknown. Recent studies have been focused on the integration of miRNA and mRNA expression to reveal the underlying biological pathways and mechanisms responsible for disease manifestation. We proposed a novel approach for integrative analysis of miRNA and mRNA expression data and developed MIMR (Integrative Analysis of miRNA and mRNA), a web-based application that leverages the Random Walk with Restart (RWR) algorithm. MIMR incorporates both direct and indirect interactions by utilizing protein\u2013protein interaction (PPI) networks and experimentally validated mRNA\u2013miRNA target interactions. MIMR provides comprehensive results, including novel pathological pathways associated with a specific disease and interactive network diagrams representing the mRNAs and miRNAs. We applied it to Alzheimer and breast cancer data and successfully identified the novel biological pathways related to these diseases. In summary, MIMR will offer a deeper insight into the hidden mechanisms of diseases and identify potential therapeutic strategies through integrated analysis of miRNAs and mRNAs.<\/jats:p>","DOI":"10.3390\/ijms252111819","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T03:57:34Z","timestamp":1730692654000},"page":"11819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MIMR: Development of a Web-Based System for miRNA and mRNA Integrated Analysis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5801-7669","authenticated-orcid":false,"given":"Dayeon","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 17035, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younhee","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 17035, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s13105-010-0050-6","article-title":"Biological functions of microRNAs: A review","volume":"67","author":"Huang","year":"2011","journal-title":"J. Physiol. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4110\/in.2011.11.3.135","article-title":"MicroRNAs in Human Diseases: From Cancer to Cardiovascular Disease","volume":"11","author":"Ha","year":"2011","journal-title":"Immune Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"W356","DOI":"10.1093\/nar\/gkp294","article-title":"MicroRNA and mRNA integrated analysis (MMIA): A web tool for examining biological functions of microRNA expression","volume":"37","author":"Nam","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"D252","DOI":"10.1093\/nar\/gks1168","article-title":"MiRGator v3. 0: A microRNA portal for deep sequencing, expression profiling and mRNA targeting","volume":"41","author":"Cho","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"W319","DOI":"10.1093\/nar\/gkad392","article-title":"miEAA 2023: Updates, new functional microRNA sets and improved enrichment visualizations","volume":"51","author":"Hirsch","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gkaa467","article-title":"miRNet 2.0: Network-based visual analytics for miRNA functional analysis and systems biology","volume":"48","author":"Chang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.3892\/mmr.2020.11162","article-title":"Integrated analysis of miRNA and mRNA expression in the blood of patients with Alzheimer\u2019s disease","volume":"22","author":"Wang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yu, W., Yang, Y., and L\u00fc, Y. (2021). Exploring the Key Genes and Identification of Potential Diagnosis Biomarkers in Alzheimer\u2019s Disease Using Bioinformatics Analysis. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.602781"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nature02621","article-title":"Pathways towards and away from Alzheimer\u2019s disease","volume":"430","author":"Mattson","year":"2004","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.24272\/j.issn.2095-8137.2023.294","article-title":"Targeting autophagy in Alzheimer\u2019s disease: Animal models and mechanisms","volume":"44","author":"Zhang","year":"2023","journal-title":"Zool. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Muguruma, Y., Tsutsui, H., Akatsu, H., and Inoue, K. (2020). Comprehensive quantification of purine and pyrimidine metabolism in Alzheimer\u2019s disease postmortem cerebrospinal fluid by LC-MS\/MS with metal-free column. Biomed. Chromatogr., 34.","DOI":"10.1002\/bmc.4722"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/2213346110666221230113833","article-title":"Bioactive Heterocycles: Green Synthesis and its Anti-Alzheimer Activity","volume":"10","author":"Aazath","year":"2023","journal-title":"Curr. Green Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Savonije, K., and Weaver, D.F. (2023). The Role of Tryptophan Metabolism in Alzheimer\u2019s Disease. Brain Sci., 13.","DOI":"10.3390\/brainsci13020292"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3934\/Neuroscience.2021005","article-title":"The biological pathways of Alzheimer disease: A review","volume":"8","author":"Rinaldi","year":"2021","journal-title":"AIMS Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bbi.2021.03.013","article-title":"Inhibition of Smad3 in macrophages promotes A\u03b2 efflux from the brain and thereby ameliorates Alzheimer\u2019s pathology","volume":"95","author":"Xu","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D1397","DOI":"10.1093\/nar\/gkac814","article-title":"RNADisease v4.0: An updated resource of RNA-associated diseases, providing RNA-disease analysis, enrichment and prediction","volume":"51","author":"Chen","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"baq020","DOI":"10.1093\/database\/baq020","article-title":"GeneCards Version 3: The human gene integrator","volume":"2010","author":"Safran","year":"2010","journal-title":"Database"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1634\/theoncologist.2017-0423","article-title":"Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance","volume":"23","author":"Brufsky","year":"2018","journal-title":"Oncologist"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10911-008-9083-7","article-title":"ERBB3\/HER3 and ERBB2\/HER2 duet in mammary development and breast cancer","volume":"13","author":"Stern","year":"2008","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mce.2011.10.030","article-title":"The biology of progesterone receptor in the normal mammary gland and in breast cancer","volume":"357","author":"Obr","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kalinina, T., Kononchuk, V., Alekseenok, E., Abdullin, G., Sidorov, S., Ovchinnikov, V., and Gulyaeva, L. (2021). Associations between the Levels of Estradiol-, Progesterone-, and Testosterone-Sensitive MiRNAs and Main Clinicopathologic Features of Breast Cancer. J. Pers. Med., 12.","DOI":"10.3390\/jpm12010004"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kalinina, T., Kononchuk, V., Klyushova, L., and Gulyaeva, L. (2022). Effects of Endocrine Disruptors o,p\u2032-Dichlorodiphenyltrichloroethane, p,p\u2032-Dichlorodiphenyltrichloroethane, and Endosulfan on the Expression of Estradiol-, Progesterone-, and Testosterone-Responsive MicroRNAs and Their Target Genes in MCF-7 Cells. Toxics, 10.","DOI":"10.3390\/toxics10010025"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D239","DOI":"10.1093\/nar\/gkx1141","article-title":"DIANA-TarBase v8: A decade-long collection of experimentally supported miRNA-gene interactions","volume":"46","author":"Karagkouni","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_26","first-page":"D148","article-title":"miRTarBase 2020: Updates to the experimentally validated microRNA-target interaction database","volume":"48","author":"Huang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Seo, J., Jung, H., and Ko, Y. (2023). PRID: Prediction Model Using RWR for Interactions between Drugs. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102469"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11819\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:27:55Z","timestamp":1760113675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":31,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111819"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111819","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,4]]}}}