{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:53:42Z","timestamp":1781520822121,"version":"3.54.1"},"reference-count":124,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Microinflammation serves as a central mechanism linking metabolic diseases and cancer. This study integrates gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC) to identify shared molecular drivers of inflammation-mediated pathology. Weighted gene co-expression network analysis (WGCNA) revealed three highly preserved modules (blue, brown, turquoise) enriched in RNA processing, spliceosome assembly, ribosome biogenesis, and proteostasis regulation. Key hub genes, along with regulatory miRNAs have interconnected networks that modulate transcription, mRNA maturation, protein synthesis, and inflammatory signaling. Although classical inflammatory pathways were not directly enriched, their activity appears to be indirectly shaped by disruptions in RNA-processing and proteostasis machinery. Additionally, gut microbiota-derived products and altered metabolic states may further reinforce these transcriptional and post-transcriptional imbalances. Collectively, these findings reveal conserved molecular signatures that bridge microinflammation, metabolic disease, and oncogenesis, and highlight potential diagnostic and therapeutic targets centered on RNA regulation, proteostasis, and miRNA-mediated control<\/jats:p>","DOI":"10.3390\/biology15010019","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T08:35:27Z","timestamp":1766392527000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microinflammation-Driven Gene Expression Dynamics in the Pathogenesis of Metabolic Disorders and Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Marian Elisa Gabrielle T.","family":"Cadungog","sequence":"first","affiliation":[{"name":"School of Chemical, Biological, and Materials Engineering and Sciences, Map\u00faa University, Manila 1002, Philippines"},{"name":"School of Graduate Studies, Map\u00faa University, Manila 1002, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lemmuel L.","family":"Tayo","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Health Sciences, Map\u00faa University, Makati 1203, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S2468-1253(20)30217-X","article-title":"Global prevalence of irritable bowel syndrome according to Rome criteria: A systematic review and meta-analysis","volume":"5","author":"Oka","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_2","unstructured":"World Health Organization (2025, September 03). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.diabres.2014.04.006","article-title":"Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes","volume":"105","author":"Esser","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_5","first-page":"1537","article-title":"miR-16 and miR-125b Are Involved in Barrier Function Dysregulation through Modulation of Claudin-2 and Cingulin Expression in the Jejunum in IBS with Diarrhoea","volume":"66","author":"Lobo","year":"2017","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The intestinal microbiota fuel metabolic inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrc3215","article-title":"The insulin and insulin-like growth factor receptor family in neoplasia: An update","volume":"12","author":"Pollak","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1053\/gast.2001.21908","article-title":"Management of irritable bowel syndrome","volume":"120","author":"Camilleri","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0140-6736(17)33102-1","article-title":"Primary care-led weight management for remission of type 2 diabetes (DiRECT): An open-label, cluster-randomised trial","volume":"391","author":"Lean","year":"2018","journal-title":"Lancet"},{"key":"ref_10","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"79","DOI":"10.14740\/wjon1279","article-title":"Epidemiology of renal cell carcinoma","volume":"11","author":"Padala","year":"2020","journal-title":"World J. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14740\/wjon1166","article-title":"Epidemiology of pancreatic cancer: Global trends, etiology and risk factors","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrd2589","article-title":"Fatty acid-binding proteins: Role in metabolic diseases and potential as drug targets","volume":"7","author":"Furuhashi","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the human gut microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.molcel.2012.08.033","article-title":"The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation","volume":"48","author":"Donohoe","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S233","DOI":"10.2337\/dcS13-2001","article-title":"Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer","volume":"36","author":"Gallagher","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nrgastro.2015.121","article-title":"Towards a systems view of IBS","volume":"12","author":"Mayer","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1056\/NEJMra1607547","article-title":"Irritable bowel syndrome","volume":"376","author":"Ford","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the ADA and EASD","volume":"45","author":"Davies","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1200\/JCO.2016.72.1985","article-title":"Safety and efficacy of nivolumab in combination with sunitinib, pazopanib, or ipilimumab in advanced renal cell carcinoma: The CheckMate 016 study","volume":"35","author":"Hammers","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gku631","article-title":"The multiMiR R package and database: Integration of microRNA\u2013target interactions along with their disease and drug associations","volume":"42","author":"Ru","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_24","unstructured":"Hol\u00fd, P., and Andrlov\u00e1, H. (2023). Integrative analysis of mRNA and miRNA expression reveals correlated pairs and disease associations. BMC Genom., 24."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e70038","DOI":"10.1096\/fj.202401464R","article-title":"MicroRNAs in metabolic dysfunction-associated diseases: Pathogenesis and therapeutic opportunities","volume":"38","author":"Ma","year":"2024","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zanoaga, O., \u0218tefan, S., and Marcu, A. (2021). The role of miR-155 in nutrition: Modulating cancer\u2013obesity\u2013immune response. Nutrients, 13.","DOI":"10.3390\/nu13072245"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sychowski, G., Romanowicz, H., Ciesielski, W., Hogendorf, P., Durczy\u0144ski, A., and Smolarz, B. (2025). Diagnostic and Therapeutic Potential of Selected microRNAs in Colorectal Cancer: A Literature Review. Cancers, 17.","DOI":"10.3390\/cancers17132135"},{"key":"ref_28","first-page":"100","article-title":"Crosstalk between miRNAs\/lncRNAs and PI3K\/AKT signaling pathway and their importance","volume":"9","year":"2024","journal-title":"Non-Coding RNA Res."},{"key":"ref_29","first-page":"506","article-title":"NF-\u03baB signaling and miRNA in cancer","volume":"19","author":"Liu","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_30","first-page":"145618","article-title":"The emerging role of non-coding RNAs in the regulation of the PI3K\/AKT pathway","volume":"784","author":"Bashiri","year":"2021","journal-title":"Gene"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Suratos, K.S., Orda, M.A., Tsai, P.-W., and Tayo, L.L. (2024). Signaling pathways in clear cell renal cell carcinoma and candidate drugs unveiled through transcriptomic network analysis of hub genes. Appl. Sci., 14.","DOI":"10.3390\/app14198768"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Barretto, A.J.B., Orda, M.A., Tsai, P.-W., and Tayo, L.L. (2024). Analysis of modular hub genes and therapeutic targets across stages of non-small cell lung cancer transcriptome. Genes, 15.","DOI":"10.3390\/genes15101248"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pasamba, E.C., Orda, M.A., Villanueva, B.H.A., Tsai, P.-W., and Tayo, L.L. (2024). Transcriptomic analysis of hub genes reveals associated inflammatory pathways in estrogen-dependent gynecological diseases. Biology, 13.","DOI":"10.3390\/biology13060397"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mailem, R.C., and Tayo, L.L. (2022). Drug repurposing using gene co-expression and module preservation analysis in ARDS, SIRS, sepsis, and COVID-19. Biology, 11.","DOI":"10.3390\/biology11121827"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Garcia, J.P.T., and Tayo, L.L. (2024). Theoretical studies of DNA microarray present potential molecular and cellular interconnectivity of signaling pathways in immune system dysregulation. Genes, 15.","DOI":"10.3390\/genes15040393"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"De La Cerna, J.L.O., Talubo, N.D.D., Villanueva, B.H.A., Tsai, P.-W., and Tayo, L.L. (2025). Conserved blood transcriptome patterns highlight microRNA and hub gene drivers of neurodegeneration. Genes, 16.","DOI":"10.3390\/genes16101178"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Garcia, J.P.T., and Tayo, L.L. (2024). Codes between poles: Linking transcriptomic insights into the neurobiology of bipolar disorder. Biology, 13.","DOI":"10.3390\/biology13100787"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Talubo, N.D.D., Tsai, P.-W., and Tayo, L.L. (2024). Comprehensive RNA-Seq gene co-expression analysis identifies shared pathways and hub genes across hepatocellular carcinoma cohorts. Biology, 13.","DOI":"10.3390\/biology13100765"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Manuel, M.T.A., and Tayo, L.L. (2023). Navigating the gene co-expression network and drug repurposing opportunities for brain disorders associated with neurocognitive impairment. Brain Sci., 13.","DOI":"10.3390\/brainsci13111564"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Villanueva, B.H.A., Tsai, P.-W., and Tayo, L.L. (2023). Analysis of gene expression networks in primary central nervous system tumors for drug repurposing prospects. Preprints, 2023082027.","DOI":"10.20944\/preprints202308.2027.v1"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Malfitano, A.M., Pisanti, S., Napolitano, F., Di Somma, S., Martinelli, R., and Portella, G. (2020). Tumor microenvironment and inflammation: A dangerous symbiosis for cancer progression. Cancers, 12.","DOI":"10.3390\/cancers12071987"},{"key":"ref_42","first-page":"315","article-title":"Inflammation and cancer: Triggers, mechanisms, and consequences","volume":"19","author":"Greten","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","first-page":"4471","article-title":"The role of inflammation in angiogenesis","volume":"20","author":"Ribatti","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref_44","first-page":"599","article-title":"Splicing-factor alterations in cancers","volume":"16","author":"Krainer","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","first-page":"597","article-title":"Alternative-splicing deregulation in cancer","volume":"15","author":"Urbanski","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13073-015-0168-9","article-title":"Widespread intron retention diversifies most cancer transcriptomes","volume":"7","author":"Dvinge","year":"2015","journal-title":"Genome Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1242\/jcs.132605","article-title":"HSF1 at a glance","volume":"127","author":"Vihervaara","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_48","first-page":"562","article-title":"Targeting the heat shock factor 1 pathway in cancer","volume":"10","author":"Workman","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.tcb.2015.10.011","article-title":"HSF1: Guardian of proteostasis in cancer","volume":"26","author":"Dai","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrc.2017.104","article-title":"Ribosome biogenesis in cancer: New players and therapeutic avenues","volume":"18","author":"Pelletier","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Penzo, M., and Montanaro, L. (2019). The ribosome biogenesis\u2013cancer connection. Cells, 8.","DOI":"10.3390\/cells8010055"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STAT3 in cancer inflammation and immunity","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri.2017.142","article-title":"NF-\u03baB, inflammation, immunity and cancer","volume":"18","author":"Taniguchi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","unstructured":"Liu, B., Tian, Y., and Li, F. (2023). Crosstalk between ER stress and inflammation: Molecular mechanisms and therapeutic outlook. Front. Immunol., 14."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gupta, S., Silveira, D.A., Lorenzoni, P.R., Carlos, J., and Hashimoto, R.F. (2024). LncRNA PTENP1\/MiR-21\/PTEN Axis Modulates EMT and Drug Resistance in Cancer: Dynamic Boolean Modeling for Cell Fates in DNA Damage Response. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158264"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chen, C., Demirkhanyan, L., and Gondi, C.S. (2024). The Multifaceted Role of MiR-21 in Pancreatic Cancers. Cells, 13.","DOI":"10.3390\/cells13110948"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s12957-022-02706-y","article-title":"Hypoxic Lung Cancer Cell-Derived Exosomal MiR-21 Mediates Macrophage M2 Polarization and Promotes Cancer Cell Proliferation through Targeting IRF1","volume":"20","author":"Jin","year":"2022","journal-title":"World J. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.tcb.2008.07.007","article-title":"The let-7 family of microRNAs","volume":"18","author":"Roush","year":"2008","journal-title":"Trends Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2005.01.014","article-title":"RAS Is Regulated by the Let-7 MicroRNA Family","volume":"120","author":"Johnson","year":"2005","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2009.10.014","article-title":"An epigenetic switch involving NF-\u03baB, Lin28, let-7 microRNA, and IL-6 links inflammation to cell transformation","volume":"139","author":"Iliopoulos","year":"2009","journal-title":"Cell"},{"key":"ref_61","first-page":"123","article-title":"Inflammatory mechanisms linking obesity and metabolic disease","volume":"8","author":"Saltiel","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"100585","DOI":"10.1016\/j.obmed.2025.100585","article-title":"Cytokines as key players in obesity low-grade inflammation and related complications","volume":"54","author":"Uti","year":"2025","journal-title":"Obes. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2147\/JIR.S174982","article-title":"The role of inflammation in irritable bowel syndrome (IBS)","volume":"11","author":"Ng","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2263209","DOI":"10.1080\/19490976.2023.2263209","article-title":"Low-level inflammation, immunity, and brain\u2013gut axis in IBS: Unraveling the complex relationships","volume":"15","author":"Yuan","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Passacatini, L.C., Ilari, S., Nucera, S., Scarano, F., Macr\u00ec, R., Caminiti, R., Serra, M., Oppedisano, F., Maiuolo, J., and Palma, E. (2024). Multiple aspects of irritable bowel syndrome and the role of the immune system: An overview of systematic reviews with a focus on polyphenols. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252211993"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: A revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_67","first-page":"8927","article-title":"Ubiquitin\u2013proteasome system in cancer development and therapy","volume":"22","author":"Komorowska","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/cr500452k","article-title":"Protein lysine acetylation by EP300\/CBP","volume":"115","author":"Dancy","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cell.2018.04.033","article-title":"Time-resolved analysis reveals rapid dynamics and broad scope of the CBP\/p300 acetylome","volume":"174","author":"Weinert","year":"2018","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/emmm.201100209","article-title":"microRNA dysregulation in cancer: Diagnostics, monitoring, and therapeutics","volume":"4","author":"Iorio","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nrd3823","article-title":"The spliceosome as a target of novel antitumour drugs","volume":"11","author":"Bonnal","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrg.2015.3","article-title":"RNA mis-splicing in disease","volume":"17","author":"Scotti","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.tibs.2008.11.004","article-title":"Cellular stress and RNA splicing","volume":"34","author":"Biamonti","year":"2009","journal-title":"Trends Biochem. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cytogfr.2025.01.003","article-title":"Insights into IL-6\/JAK\/STAT3 Signaling in the Tumor Microenvironment: Implications for Cancer Therapy","volume":"85","author":"Thuya","year":"2025","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/mco2.104","article-title":"NF-\u039aB Signaling in Inflammation and Cancer","volume":"2","author":"Zhang","year":"2021","journal-title":"MedComm"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"33","DOI":"10.21037\/tbcr-24-29","article-title":"Regulation of PI3K Signaling in Cancer Metabolism and PI3K-Targeting Therapy","volume":"5","author":"Han","year":"2024","journal-title":"Transl. Breast Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"189207","DOI":"10.1016\/j.bbcan.2024.189207","article-title":"Structure, Function, Signaling Pathways and Clinical Therapeutics: The Translational Potential of STAT3 as a Target for Cancer Therapy","volume":"1879","author":"Shi","year":"2024","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mitoco.2024.01.001","article-title":"Structural Determinants of Mitochondrial STAT3 Targeting and Function","volume":"2","author":"Lahiri","year":"2024","journal-title":"Mitochondrial Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s10020-025-01246-x","article-title":"JAK2\/STAT3\/HMGCS2 Signaling Aggravates Mitochondrial Dysfunction and Oxidative Stress in Hyperuricemia-Induced Cardiac Dysfunction","volume":"31","author":"Peng","year":"2025","journal-title":"Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12944-025-02612-8","article-title":"Unlocking the Lipid Code: SREBPs as Key Drivers in Gastrointestinal Tumour Metabolism","volume":"24","author":"Tang","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"188952","DOI":"10.1016\/j.bbcan.2023.188952","article-title":"PI3K Signaling-Regulated Metabolic Reprogramming: From Mechanism to Application","volume":"1878","author":"Su","year":"2023","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40164-024-00529-z","article-title":"Versatile function of NF-\u03baB in inflammation and cancer","volume":"13","author":"Ma","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"104844","DOI":"10.1016\/j.critrevonc.2025.104844","article-title":"Novel Insight into the Warburg Effect: Sweet Temptation","volume":"214","author":"Zhang","year":"2025","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e70948","DOI":"10.1002\/cam4.70948","article-title":"Advances in the Study of Metabolic Reprogramming in Gastric Cancer","volume":"14","author":"Rong","year":"2025","journal-title":"Cancer Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.apsb.2023.12.003","article-title":"Targeting the Warburg Effect: A Revisited Perspective from Molecular Mechanisms to Traditional and Innovative Therapeutic Strategies in Cancer","volume":"14","author":"Liao","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"100901","DOI":"10.1016\/j.bbih.2024.100901","article-title":"Targeting Glycolysis for Neuroprotection in Early LPS-Induced Neuroinflammation","volume":"42","author":"Vizuete","year":"2024","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41420-025-02623-5","article-title":"Metabolic Reprogramming in Colorectal Cancer: A Review of Aerobic Glycolysis and Its Therapeutic Implications for Targeted Treatment Strategies","volume":"11","author":"Pang","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Korsten, S.G.P.J., Vromans, H., Garssen, J., and Willemsen, L.E.M. (2023). Butyrate Protects Barrier Integrity and Suppresses Immune Activation in a Caco-2\/PBMC Co-Culture Model While HDAC Inhibition Mimics Butyrate in Restoring Cytokine-Induced Barrier Disruption. Nutrients, 15.","DOI":"10.3390\/nu15122760"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Chen, W., Ma, Q., Li, Y., Wei, L., Zhang, Z., Khan, A., Khan, M.Z., and Wang, C. (2025). Butyrate Supplementation Improves Intestinal Health and Growth Performance in Livestock: A Review. Biomolecules, 15.","DOI":"10.3390\/biom15010085"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wang, K., Lai, W., Min, T., Wei, J., Bai, Y., Cao, H., Guo, J., and Su, Z. (2024). The Effect of Enteric-Derived Lipopolysaccharides on Obesity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084305"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e162291","DOI":"10.1172\/JCI162291","article-title":"Effect of Acute TLR4 Inhibition on Insulin Resistance in Humans","volume":"132","author":"Liang","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s13098-025-01847-w","article-title":"Serum Lipopolysaccharide Binding Protein (LBP) and Metabolic Syndrome: A Systematic Review and Meta-Analysis","volume":"17","author":"Rezaei","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1038\/s41467-022-30489-z","article-title":"RNA Splicing Is a Key Mediator of Tumour Cell Plasticity and a Therapeutic Vulnerability in Colorectal Cancer","volume":"13","author":"Hall","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Zhang, S., Zhang, Y., Feng, S., Han, M., Wang, Z., Qiao, D., Tian, J., Wang, L., Du, B., and Zhang, Z. (2025). Tumor-Promoting Effect and Tumor Immunity of SRSFs. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1527309"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s11658-024-00594-6","article-title":"SR Proteins in Cancer: Function, Regulation, and Small Inhibitor","volume":"29","author":"Bei","year":"2024","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Sharma, S., Mittal, M., Shukla, A., Khan, J., Dinand, V., and Saluja, D. (2024). Exploring Serine-Arginine Rich Splicing Factors: Potential Predictive Markers for Dysregulation in Oral Cancer. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12750-4"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Borz, M.B., Fetica, B., Gliga, M.C., Sipos, T.-C., Buhas, B.A., and Schitcu, V.H. (2025). PTEN and ERG Biomarkers as Predictors of Biochemical Recurrence Risk in Patients Undergoing Radical Prostatectomy. Diseases, 13.","DOI":"10.3390\/diseases13080235"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3390\/applbiosci2030029","article-title":"Deregulations of RNA Pol II Subunits in Cancer","volume":"2","author":"Sadurni","year":"2023","journal-title":"Appl. Biosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1186\/s12967-025-06929-x","article-title":"Atypical R-Loops in Cancer: Decoding Molecular Chaos for Therapeutic Gain","volume":"23","author":"Sun","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.2147\/JIR.S496748","article-title":"Comprehensive Analysis of Multi-Omics Data on RNA Polymerase as an Adverse Factor in Head and Neck Squamous Cell Carcinoma","volume":"18","author":"Gu","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"AlZaabi, A., and Shalaby, A. (2024). A Systematic Review of Diagnostic Performance of Circulating MicroRNAs in Colorectal Cancer Detection with a Focus on Early-Onset Colorectal Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179565"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Fathi, S., Aazzane, O., Guendaoui, S., Tawfiq, N., Sahraoui, S., Guessous, F., and Karkouri, M. (2025). A MiRNA Signature for Non-Invasive Colorectal Cancer Diagnosis in Morocco: MiR-21, MiR-29a and MiR-92a. Non-Coding RNA, 11.","DOI":"10.3390\/ncrna11020026"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Schwab, S., and Nonaka, T. (2025). Circulating MiRNAs as Liquid Biopsy Biomarkers for Diagnosis in Patients with Colorectal Cancer: A Systematic Review and Meta-Analysis. Front. Genet., 16.","DOI":"10.3389\/fgene.2025.1574586"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"28597","DOI":"10.1038\/s41598-025-14485-z","article-title":"A Preliminary Assessment of a Stool-Based MicroRNA Profile for Early Colorectal Cancer Screening","volume":"15","author":"Santos","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"9491","DOI":"10.1038\/s41598-019-45570-9","article-title":"Christos Polytarchou Faecal MicroRNAs as a Non-Invasive Tool in the Diagnosis of Colonic Adenomas and Colorectal Cancer: A Meta-Analysis","volume":"9","author":"Yau","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12964-023-01433-5","article-title":"Interplay between Proteasome Inhibitors and NF-\u039aB Pathway in Leukemia and Lymphoma: A Comprehensive Review on Challenges ahead of Proteasome Inhibitors","volume":"22","author":"Pakjoo","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"123125","DOI":"10.1016\/j.lfs.2024.123125","article-title":"Bortezomib in Cancer Therapy: Mechanisms, Side Effects, and Future Proteasome Inhibitors","volume":"358","author":"Sogbein","year":"2024","journal-title":"Life Sci."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Pelon, M., Krzeminski, P., Tracz-Gaszewska, Z., and Misiewicz-Krzeminska, I. (2024). Factors Determining the Sensitivity to Proteasome Inhibitors of Multiple Myeloma Cells. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1351565"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"S3084","DOI":"10.21037\/jtd.2018.07.50","article-title":"Interleukin-1 Beta Inhibition with Canakinumab and Reducing Lung Cancer\u2014Subset Analysis of the Canakinumab Anti-Inflammatory Thrombosis Outcome Study Trial (CANTOS)","volume":"10","author":"Crossman","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41416-022-01893-5","article-title":"Repositioning Canakinumab for Non-Small Cell Lung Cancer\u2014Important Lessons for Drug Repurposing in Oncology","volume":"127","author":"Lythgoe","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1002\/jcsm.13638","article-title":"Tocilizumab for Advanced Non-Small-Cell Lung Cancer with Concomitant Cachexia: An Observational Study","volume":"15","author":"Du","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1200\/JCO.23.01965","article-title":"Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine with or without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia","volume":"43","author":"Chen","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"155976","DOI":"10.1016\/j.cyto.2022.155976","article-title":"Blockade of IL-6 Inhibits Tumor Immune Evasion and Improves Anti\u2013PD-1 Immunotherapy","volume":"158","author":"Li","year":"2022","journal-title":"Cytokine"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Rangraze, I., Wali, A.F., El-Tanani, M., Patni, M.A., Rabbani, S.A., Babiker, R., Satyam, S.M., El-Tanani, Y., and Rizzo, M. (2025). Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis. Medicina, 61.","DOI":"10.3390\/medicina61061021"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Wang, J., Lin, J., Guo, H., Wu, W., Yang, J., Mao, J., Fan, W., Qiao, H., Wang, Y., and Yan, X. (2024). Prognostic Impact of Metformin in Solid Cancer Patients Receiving Immune Checkpoint Inhibitors: Novel Evidences from a Multicenter Retrospective Study. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1419498"},{"key":"ref_117","first-page":"1","article-title":"Metformin and Anti-Cancer Effects: Systematic Insights into Its Therapeutic Potential","volume":"18","author":"Ramesh","year":"2024","journal-title":"Oncol. Radiother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/S0140-6736(23)00913-3","article-title":"Adjuvant Everolimus after Surgery for Renal Cell Carcinoma (EVEREST): A Double-Blind, Placebo-Controlled, Randomised, Phase 3 Trial","volume":"402","author":"Ryan","year":"2023","journal-title":"Lancet"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1056\/NEJMoa2313906","article-title":"Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma","volume":"391","author":"Choueiri","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Seyhan, A.A. (2024). Trials and Tribulations of MicroRNA Therapeutics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031469"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"995","DOI":"10.2215\/CJN.0000000000000458","article-title":"A Randomized Controlled Clinical Trial Testing Effects of Lademirsen on Kidney Function Decline in Adults with Alport Syndrome","volume":"19","author":"Gale","year":"2024","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1089\/hum.2024.113","article-title":"Advances in MicroRNA Therapeutics: From Preclinical to Clinical Studies","volume":"35","author":"Brillante","year":"2024","journal-title":"Hum. Gene Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13046-025-03391-x","article-title":"MicroRNA in cancer therapy: Breakthroughs and challenges in early clinical applications","volume":"44","author":"Tagliaferri","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Wang, H. (2024). Nanotechnology in microRNA Detection and Delivery. Cells, 13.","DOI":"10.3390\/cells13151277"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/1\/19\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T05:12:14Z","timestamp":1766639534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/1\/19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,21]]},"references-count":124,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biology15010019"],"URL":"https:\/\/doi.org\/10.3390\/biology15010019","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,21]]}}}