{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:34:50Z","timestamp":1771104890806,"version":"3.50.1"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>MicroRNAs (miRNAs) regulate gene expression and play an important role in carcinogenesis through complex interactions with messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Despite their established influence on tumor progression and therapeutic resistance, the application of miRNA interaction networks for tumor tissue-of-origin (TOO) classification remains underexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a machine learning (ML) framework that integrates miRNA-mRNA-lncRNA interaction networks to classify tumors by their tissue of origin. Using transcriptomic profiles from 14 cancer types in The Cancer Genome Atlas (TCGA), we constructed co-expression networks and applied multiple feature selection techniques including recursive feature elimination (RFE), random forest (RF), Boruta, and linear discriminant analysis (LDA) to identify a minimal yet informative subset of miRNA features. Ensemble ML algorithms were trained and validated with stratified five-fold cross-validation for robust performance assessment across class distributions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our models achieved an overall 99% classification accuracy, distinguishing 14 cancer types with high robustness and generalizability. A minimal set of 150 miRNAs selected via RFE resulted in optimal performance across all classifiers. Furthermore, in silico validation revealed that many of the top miRNAs, including <jats:italic>miR-21-5p, miR-93-5p,<\/jats:italic> and <jats:italic>miR-10b-5p<\/jats:italic>, were not only highly central in the network but also correlated with patient survival and drug response. In addition, functional enrichment analyses indicated significant involvement of miRNAs in pathways such as <jats:italic>TGF<\/jats:italic>-beta signaling, epithelial-mesenchymal transition, and immune modulation. Our comparative analysis demonstrated that models based on miRNA outperformed those using mRNA or lncRNA classifiers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our integrated framework provides a biologically grounded, interpretable, and highly accurate approach for tumor tissue-of-origin classification. The identified miRNA biomarkers demonstrate strong translational potential, supported by clinical trial overlap, drug sensitivity data, and survival analyses. This work highlights the power of combining miRNA network biology with ML to improve precision oncology diagnostics and supports future development of liquid biopsy-based cancer classification.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbinf.2025.1571476","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T04:16:07Z","timestamp":1746504967000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Tumor tissue-of-origin classification using miRNA-mRNA-lncRNA interaction networks and machine learning methods"],"prefix":"10.3389","volume":"5","author":[{"given":"Ankita","family":"Lawarde","sequence":"first","affiliation":[]},{"given":"Masuma","family":"Khatun","sequence":"additional","affiliation":[]},{"given":"Prakash","family":"Lingasamy","sequence":"additional","affiliation":[]},{"given":"Andres","family":"Salumets","sequence":"additional","affiliation":[]},{"given":"Vijayachitra","family":"Modhukur","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4958","DOI":"10.1093\/nar\/gkz250","article-title":"Discovering sequence and structure landscapes in RNA interaction motifs","volume":"47","author":"Adinolfi","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5546","DOI":"10.3390\/cancers13215546","article-title":"State-of-the-art challenges and perspectives in multi-organ cancer diagnosis via deep learning-based methods","volume":"13","author":"Ali","year":"2021","journal-title":"Cancers (Basel)."},{"key":"B3","doi-asserted-by":"publisher","first-page":"46101","DOI":"10.1038\/srep46101","article-title":"Novel miRNA-mRNA interactions conserved in essential cancer pathways","volume":"7","author":"Andr\u00e9s-Le\u00f3n","year":"2017","journal-title":"Sci. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.7324\/JAPS.2023.175392","article-title":"Coregulatory mechanism and interactome network of miRNA, lncRNA, and mRNA involved in human diseases","volume":"14","author":"Archit","year":"2024","journal-title":"J. Appl. Pharm. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"D149","DOI":"10.1093\/nar\/gkm995","article-title":"The microRNA.org resource: targets and expression","volume":"36","author":"Betel","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"954926","DOI":"10.3389\/fmolb.2022.954926","article-title":"Computational tools to study RNA-protein complexes","volume":"9","author":"Bheemireddy","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"10253","DOI":"10.18632\/oncotarget.3520","article-title":"Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer","volume":"6","author":"Bovy","year":"2015","journal-title":"Oncotarget"},{"key":"B8","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6719","DOI":"10.3390\/ijms25126719","article-title":"Biomarkers in thyroid cancer: emerging opportunities from non-coding RNAs and mitochondrial space","volume":"25","author":"Caban\u00e9","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"goac064","DOI":"10.1093\/gastro\/goac064","article-title":"Artificial intelligence in gastric cancer: applications and challenges","volume":"10","author":"Cao","year":"2022","journal-title":"Gastroenterol. Rep. (Oxf)."},{"key":"B11","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s11658-024-00632-3","article-title":"MicroRNAs in metabolism for precision treatment of lung cancer","volume":"29","author":"Carr\u00e0","year":"2024","journal-title":"Cell. Mol. Biol. Lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.3390\/genes14071375","article-title":"miRNAs: potential as biomarkers and therapeutic targets for cancer","volume":"14","author":"Chakrabortty","year":"2023","journal-title":"Genes (Basel)."},{"key":"B13","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12859-016-1421-y","article-title":"MicroRNA based pan-cancer diagnosis and treatment recommendation","volume":"18","author":"Cheerla","year":"2017","journal-title":"BMC Bioinforma."},{"key":"B14","doi-asserted-by":"publisher","first-page":"646192","DOI":"10.3389\/fonc.2021.646192","article-title":"Roles of non-coding RNAs in cervical cancer metastasis","volume":"11","author":"Cheng","year":"2021","journal-title":"Front. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"805","DOI":"10.14348\/molcells.2017.0241","article-title":"Phospholipase D and its essential role in cancer","volume":"40","author":"Cho","year":"2017","journal-title":"Korean Soc. Mol. Cell. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"eaay9040","DOI":"10.1126\/science.aay9040","article-title":"Early detection of cancer","volume":"375","author":"Crosby","year":"2022","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","first-page":"13681","DOI":"10.1074\/jbc.ra119.008619","article-title":"Triple-negative breast cancer-derived microvesicles transfer microRNA221 to the recipient cells and thereby promote epithelial-to-mesenchymal transition","volume":"294","author":"Das","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.3389\/fgene.2019.01284","article-title":"Dysregulated lncRNA-miRNA-mRNA network reveals patient survival-associated modules and RNA binding proteins in invasive breast carcinoma","volume":"10","author":"Dong","year":"2020","journal-title":"Front. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1002\/cam4.5077","article-title":"MicroRNA-204-5p: a pivotal tumor suppressor","volume":"12","author":"Fan","year":"2023","journal-title":"Cancer Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1383852","DOI":"10.3389\/fgene.2024.1383852","article-title":"Comparison of the classifiers based on mRNA, microRNA and lncRNA expression and DNA methylation profiles for the tumor origin detection","volume":"15","author":"Feng","year":"2024","journal-title":"Front. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12938-021-00857-9","article-title":"miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools","volume":"20","author":"Galv\u00e3o-Lima","year":"2021","journal-title":"Biomed. Eng. OnLine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12920-021-00918-x","article-title":"Integrated analysis of lncRNA\u2013miRNA\u2013mRNA ceRNA network and the potential prognosis indicators in sarcomas","volume":"14","author":"Gao","year":"2021","journal-title":"BMC Med. Genomics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.7150\/jca.19470","article-title":"MicroRNA-204-5p inhibits invasion and metastasis of laryngeal squamous cell carcinoma by suppressing forkhead box C1","volume":"8","author":"Gao","year":"2017","journal-title":"J. Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6588","DOI":"10.26355\/eurrev_201908_18545","article-title":"Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) promotes breast cancer progression by sponging miRNA-381","volume":"23","author":"Gao","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/carcin\/bgt337","article-title":"Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer","volume":"35","author":"Gong","year":"2014","journal-title":"Carcinogenesis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"703","DOI":"10.4161\/rna.20481","article-title":"The hallmarks of cancer: a long non-coding RNA point of view","volume":"9","author":"Gutschner","year":"2012","journal-title":"RNA Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature11404","article-title":"Comprehensive genomic characterization of squamous cell lung cancers","volume":"489","author":"Hammerman","year":"2012","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3389\/fgene.2019.00478","article-title":"The potential for microRNA therapeutics and clinical research","volume":"10","author":"Hanna","year":"2019","journal-title":"Front. Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1002\/ijc.32543","article-title":"Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma","volume":"146","author":"He","year":"2020","journal-title":"Int. J. Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41588-021-00791-5","article-title":"The NCI genomic data commons","volume":"53","author":"Heath","year":"2021","journal-title":"Nat. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.21037\/jtd-22-1449","article-title":"The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review","volume":"14","author":"Huang","year":"2022","journal-title":"J. Thorac. Dis. AME Publ. Co."},{"key":"B32","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s40364-021-00272-1","article-title":"miR-21: a non\u2010specific biomarker of all maladies","volume":"9","author":"Jenike","year":"2021","journal-title":"Biomark. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"bqae110","DOI":"10.1210\/endocr\/bqae110","article-title":"Stanniocalcin protein expression in female reproductive organs: literature review and public cancer database analysis","volume":"165","author":"Khatun","year":"2024","journal-title":"Endocrinology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1609936","DOI":"10.3389\/pore.2021.1609936","article-title":"Low expression of stanniocalcin 1 (STC-1) protein is associated with poor clinicopathologic features of endometrial cancer","volume":"27","author":"Khatun","year":"2021","journal-title":"Pathology Oncol. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1038\/s12276-023-01050-9","article-title":"MicroRNA: trends in clinical trials of cancer diagnosis and therapy strategies","volume":"55","author":"Kim","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","author":"Koboldt","year":"2012","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ncrna.2023.10.006","article-title":"ExplORRNet: an interactive web tool to explore stage-wise miRNA expression profiles and their interactions with mRNA and lncRNA in human breast and gynecological cancers","volume":"9","author":"Lawarde","year":"2024","journal-title":"Noncoding RNA Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"83913","DOI":"10.18632\/oncotarget.19996","article-title":"Selective secretion of microRNAs from lung cancer cells via extracellular vesicles promotes CAMK1D-mediated tube formation in endothelial cells","volume":"8","author":"Lawson","year":"2017","journal-title":"Oncotarget"},{"key":"B39","doi-asserted-by":"publisher","first-page":"5109","DOI":"10.1172\/jci75695","article-title":"MiR-200-containing extracellular vesicles promote breast cancer cell metastasis","volume":"124","author":"Le","year":"2014","journal-title":"J. Clin. Investigation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","article-title":"Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets","volume":"120","author":"Lewis","year":"2025","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12967-021-03215-4","article-title":"The role of Exosomal miRNAs in cancer","volume":"20","author":"Li","year":"2022","journal-title":"J. Transl. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13045-020-00849-7","article-title":"NoncoRNA: a database of experimentally supported non-coding RNAs and drug targets in cancer","volume":"13","author":"Li","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.asjsur.2016.07.001","article-title":"Tumor suppressor miRNA-204-5p promotes apoptosis by targeting BCL2 in prostate cancer cells","volume":"40","author":"Lin","year":"2017","journal-title":"Asian J. Surg."},{"key":"B44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-3-030-58174-9_2","article-title":"Homing peptides for cancer therapy","volume":"1295","author":"Lingasamy","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"119373","DOI":"10.1016\/j.biomaterials.2019.119373","article-title":"Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery","volume":"219","author":"Lingasamy","year":"2019","journal-title":"Biomaterials"},{"key":"B46","doi-asserted-by":"publisher","first-page":"9613","DOI":"10.18632\/aging.202706","article-title":"Hypoxia-induced microRNA-155 overexpression in extracellular vesicles promotes renal cell carcinoma progression by targeting FOXO3","volume":"13","author":"Liwei","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1002\/ijc.31796","article-title":"Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis","volume":"144","author":"Lopatina","year":"2019","journal-title":"Int. J. Cancer"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12071785","article-title":"Machine learning-based ensemble recursive feature selection of circulating mirnas for cancer tumor classification","volume":"12","author":"Lopez-Rincon","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4201","DOI":"10.1080\/21655979.2021.1952051","article-title":"Identification of an eleven-miRNA signature to predict the prognosis of endometrial cancer","volume":"12","author":"Lu","year":"2021","journal-title":"Bioengineered"},{"key":"B50","doi-asserted-by":"publisher","first-page":"664242","DOI":"10.3389\/fonc.2021.664242","article-title":"miR-1301-3p promotes cell proliferation and facilitates cell cycle progression via targeting SIRT1 in gastric cancer","volume":"11","author":"Luo","year":"2021","journal-title":"Front. Oncol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"pkac080","DOI":"10.1093\/jncics\/pkac080","article-title":"Prediction of tissue-of-origin of early stage cancers using serum miRNomes","volume":"7","author":"Matsuzaki","year":"2023","journal-title":"JNCI Cancer Spectr."},{"key":"B52","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.critrevonc.2015.10.003","article-title":"Exploring miRNA based approaches in cancer diagnostics and therapeutics","volume":"98","author":"Mishra","year":"2016","journal-title":"Crit. Rev. Oncology\/Hematology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/s41467-020-14713-2","article-title":"Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival","volume":"11","author":"Mitra","year":"2020","journal-title":"Nat. Commun."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2217\/epi-2017-0118","article-title":"MethSurv: a web tool to perform multivariable survival analysis using DNA methylation data","volume":"10","author":"Modhukur","year":"2018","journal-title":"Epigenomics"},{"key":"B55","doi-asserted-by":"publisher","first-page":"3768","DOI":"10.3390\/cancers13153768","article-title":"Machine learning approaches to classify primary and metastatic cancers using tissue of origin-based dna methylation profiles","volume":"13","author":"Modhukur","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B56","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/s1470-2045(24)00274-2","article-title":"Premature mortality trends in 183 countries by cancer type, sex, WHO region, and World Bank income level in 2000\u201319: a retrospective, cross-sectional, population-based study","volume":"25","author":"Murthy","year":"2024","journal-title":"Lancet Oncol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"4530","DOI":"10.1111\/jcmm.17477","article-title":"Construction of miRNA-lncRNA-mRNA co-expression network affecting EMT-mediated cisplatin resistance in ovarian cancer","volume":"26","author":"Naghsh-Nilchi","year":"2022","journal-title":"J. Cell Mol. Med."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1080\/15384101.2021.1930356","article-title":"Investigation of miR-93-5p and its effect on the radiosensitivity of breast cancer","volume":"20","author":"Pan","year":"2021","journal-title":"Cell Cycle"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1136\/gut.2009.179531","article-title":"MicroRNAs: tools for cancer diagnostics","volume":"58","author":"Paranjape","year":"2009","journal-title":"Gut"},{"key":"B60","doi-asserted-by":"publisher","first-page":"111263","DOI":"10.1016\/j.cellsig.2024.111263","article-title":"MicroRNAs in extracellular vesicles: a potential role in cancer progression","volume":"121","author":"Parashar","year":"2024","journal-title":"Cell. Signal."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.3390\/cancers14041090","article-title":"The roles of microRNAs in cancer multidrug resistance","volume":"14","author":"Pavl\u00edkov\u00e1","year":"2022","journal-title":"Cancers (Basel)."},{"key":"B62","doi-asserted-by":"publisher","first-page":"7268","DOI":"10.3390\/ijms24087268","article-title":"An overview of the role of MicroRNAs on carcinogenesis: a focus on cell cycle, angiogenesis and metastasis","volume":"24","author":"Pekarek","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"15004","DOI":"10.1038\/sigtrans.2015.4","article-title":"The role of microRNAs in human cancer","volume":"1","author":"Peng","year":"2016","journal-title":"Signal Transduct. Target. Ther."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e1764","DOI":"10.1002\/cnr2.1764","article-title":"Technological advancements in cancer diagnostics: improvements and limitations","volume":"6","author":"Pulumati","year":"2023","journal-title":"Cancer Rep. Hob."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.7150\/ijms.102123","article-title":"Decoding the promise and challenges of miRNA-based cancer therapies: an essential update on miR-21, miR-34, and miR-155","volume":"21","author":"Qian","year":"2024","journal-title":"Int. J. Med. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"102920","DOI":"10.1016\/j.amjoto.2021.102920","article-title":"miR-1301-3p suppresses tumor growth by downregulating PCNA in thyroid papillary cancer","volume":"42","author":"Qiao","year":"2021","journal-title":"Am. J. Otolaryngology - Head Neck Med. Surg."},{"key":"B67","doi-asserted-by":"publisher","first-page":"e56538","DOI":"10.2196\/56538","article-title":"Deep learning\u2013based identification of tissue of origin for carcinomas of unknown primary using MicroRNA expression: algorithm development and validation","volume":"5","author":"Raghu","year":"2024","journal-title":"JMIR Bioinform Biotech."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1233657","DOI":"10.3389\/fgene.2023.1233657","article-title":"MBMethPred: a computational framework for the accurate classification of childhood medulloblastoma subgroups using data integration and AI-based approaches","volume":"14","author":"Rahmani","year":"2023","journal-title":"Front. Genet."},{"key":"B69","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s11523-020-00717-x","article-title":"MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as new tools for cancer therapy: first steps from bench to bedside","volume":"15","author":"Ratti","year":"2020","journal-title":"Target. Oncol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.3390\/cells11182791","article-title":"From molecular mechanisms to therapeutics: understanding MicroRNA-21 in cancer","volume":"11","author":"Rhim","year":"2022","journal-title":"Cells"},{"key":"B71","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA hypothesis: the rosetta stone of a hidden RNA language?","author":"Salmena","year":"2011","journal-title":"Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"e1662","DOI":"10.1002\/wrna.1662","article-title":"microRNA-based diagnostic and therapeutic applications in cancer medicine","volume":"12","author":"Sempere","year":"2021","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.3390\/ijms25031469","article-title":"Trials and tribulations of MicroRNA therapeutics","volume":"25","author":"Seyhan","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13148-018-0587-8","article-title":"The role and mechanisms of action of microRNAs in cancer drug resistance","volume":"11","author":"Si","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"B75","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"B76","doi-asserted-by":"publisher","first-page":"10001","DOI":"10.1002\/jcb.28283","article-title":"miR-186 inhibits proliferation, migration, and epithelial-mesenchymal transition in breast cancer cells by targeting Twist1","volume":"120","author":"Sun","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1093\/nar\/gkae017","article-title":"CMC: cancer miRNA Census \u2013 a list of cancer-related miRNA genes","volume":"52","author":"Suszynska","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ebiom.2019.03.082","article-title":"Pan-cancer analysis on microRNA-associated gene activation","volume":"43","author":"Tan","year":"2019","journal-title":"EBioMedicine"},{"key":"B79","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1093\/bioinformatics\/btx622","article-title":"Tumor origin detection with tissue-specific miRNA and DNA methylation markers","volume":"34","author":"Tang","year":"2018","journal-title":"Bioinformatics"},{"key":"B80","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature12986","article-title":"The multilayered complexity of ceRNA crosstalk and competition","volume":"505","author":"Tay","year":"2014","journal-title":"Nature"},{"key":"B81","doi-asserted-by":"publisher","first-page":"100067","DOI":"10.1016\/j.xgen.2021.100067","article-title":"Molecular analysis of TCGA breast cancer histologic types","volume":"1","author":"Thennavan","year":"2021","journal-title":"Cell Genomics"},{"key":"B82","doi-asserted-by":"publisher","first-page":"A68","DOI":"10.5114\/wo.2014.47136","article-title":"Review the cancer Genome Atlas (TCGA): an immeasurable source of knowledge","author":"Tomczak","year":"2015","journal-title":"Wspolczesna Onkol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"6716","DOI":"10.1038\/ncomms7716","article-title":"Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier","volume":"6","author":"Tominaga","year":"2015","journal-title":"Nat. Commun."},{"key":"B84","doi-asserted-by":"publisher","first-page":"978840","DOI":"10.3389\/fgene.2022.978840","article-title":"miR-21-5p\/PRKCE axis implicated in immune infiltration and poor prognosis of kidney renal clear cell carcinoma","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Genet."},{"key":"B85","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.omtn.2020.03.002","article-title":"Tumor-derived EV-encapsulated miR-181b-5p induces angiogenesis to foster tumorigenesis and metastasis of ESCC","volume":"20","author":"Wang","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B86","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12943-017-0694-8","article-title":"Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p","volume":"16","author":"Wei","year":"2017","journal-title":"Mol. Cancer"},{"key":"B87","doi-asserted-by":"publisher","first-page":"248","DOI":"10.3892\/ol.2022.13368","article-title":"Serum miRNA-204-5p as a potential non-invasive biomarker for the diagnosis of endometrial cancer with sentinel lymph node mapping","volume":"24","author":"Wu","year":"2022","journal-title":"Oncol. Lett."},{"key":"B88","doi-asserted-by":"publisher","first-page":"5865","DOI":"10.3390\/ijms25115865","article-title":"How MicroRNAs command the battle against cancer","volume":"25","author":"Wu","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1016\/j.bbagen.2016.01.012","article-title":"The use of Gene Ontology terms and KEGG pathways for analysis and prediction of oncogenes","volume":"1860","author":"Xing","year":"2016","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"B90","doi-asserted-by":"publisher","first-page":"5657","DOI":"10.26355\/eurrev_201907_18302","article-title":"MicroRNA-93-5p\/IFNAR1 axis accelerates metastasis of endometrial carcinoma by activating the STAT3 pathway","volume":"23","author":"Xu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.7150\/jca.47817","article-title":"Exosomal miR-10b-5p mediates cell communication of gastric cancer cells and fibroblasts and facilitates cell proliferation","volume":"12","author":"Yan","year":"2021","journal-title":"J. Cancer"},{"key":"B92","first-page":"42","article-title":"Construction and analysis of lncRNA-miRNA-mRNA ceRNA network identify an eight-gene signature as a potential prognostic factor in kidney renal papillary cell carcinoma (KIRP)","volume":"28","author":"Yang","year":"2022","journal-title":"Altern. Ther. Health Med."},{"key":"B93","doi-asserted-by":"publisher","first-page":"100190","DOI":"10.1016\/j.xhgg.2023.100190","article-title":"Artificial intelligence-driven pan-cancer analysis reveals miRNA signatures for cancer stage prediction","volume":"4","author":"Yerukala Sathipati","year":"2023","journal-title":"Hum. Genet. Genomics Adv."},{"key":"B94","doi-asserted-by":"publisher","first-page":"286","DOI":"10.21037\/tau-22-872","article-title":"Exosomal miR-93-5p as an important driver of bladder cancer progression","volume":"12","author":"Yuan","year":"2023","journal-title":"Transl. Androl. Urol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1005522","DOI":"10.3389\/fgene.2022.1005522","article-title":"The role of lncRNA H19 in tumorigenesis and drug resistance of human Cancers","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Genet."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.3389\/fphar.2020.01112","article-title":"Construction and analysis of the tumor-specific mRNA\u2013miRNA\u2013lncRNA network in gastric cancer","volume":"11","author":"Zheng","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"e3331","DOI":"10.1002\/jgm.3331","article-title":"Long non-coding RNA ADAMTS9-AS1 inhibits the progression of prostate cancer by modulating the miR-142-5p\/CCND1 axis","volume":"23","author":"Zhou","year":"2021","journal-title":"J. Gene Med."}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1571476\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T04:16:10Z","timestamp":1746504970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1571476\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":97,"alternative-id":["10.3389\/fbinf.2025.1571476"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2025.1571476","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"article-number":"1571476"}}