{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:39:14Z","timestamp":1760060354755,"version":"build-2065373602"},"reference-count":94,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"institutional \u201cRicerca Corrente\u201d granted by the Italian Ministry of Health","award":["CUP H83C22000550006","101130740"],"award-info":[{"award-number":["CUP H83C22000550006","101130740"]}]},{"name":"European Union\u2013NextGeneration EU through the Italian Ministry of University and Research under PNRR\u2014M4C2-I1.3 Project PE_00000019 \u201cHEAL ITALIA\u201d","award":["CUP H83C22000550006","101130740"],"award-info":[{"award-number":["CUP H83C22000550006","101130740"]}]},{"name":"European Union\u2019s HORIZON.3.1\u2014The European Innovation Council (EIC)","award":["CUP H83C22000550006","101130740"],"award-info":[{"award-number":["CUP H83C22000550006","101130740"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan\u2013Meier\u2019s and Cox\u2019s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug\u2013gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p = 0.013 and p = 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p = 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r2 = 0.982, p = 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusions: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays.<\/jats:p>","DOI":"10.3390\/cancers17172768","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:26:14Z","timestamp":1756189574000},"page":"2768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulated MicroRNAs in Urinary Non-Muscle-Invasive Bladder Cancer: From Molecular Characterization to Clinical Applicability"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-6936","authenticated-orcid":false,"given":"Nouha","family":"Setti Boubaker","sequence":"first","affiliation":[{"name":"UOSD SAFU Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"},{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 Avril 1938, Tunis 1006, Tunisia"},{"name":"Laboratory of Proteins Engineering and Bioactive Molecules (LIP-MB), Biology Engineering Department, National Institute of Applied Sciences and Technology (INSAT), University of Tunis Carthage, Tunis 1080, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7661-9059","authenticated-orcid":false,"given":"Aymone","family":"Gurtner","sequence":"additional","affiliation":[{"name":"UOSD SAFU Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-6701","authenticated-orcid":false,"given":"Sami","family":"Boussetta","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Immunology and Human Pathology, Biology Department, Faculty of Science of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-0596","authenticated-orcid":false,"given":"Isabella","family":"Manni","sequence":"additional","affiliation":[{"name":"UOSD SAFU Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-9005","authenticated-orcid":false,"given":"Ahmed","family":"Saadi","sequence":"additional","affiliation":[{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 Avril 1938, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7365-0309","authenticated-orcid":false,"given":"Haroun","family":"Ayed","sequence":"additional","affiliation":[{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 Avril 1938, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2367-3852","authenticated-orcid":false,"given":"Livia","family":"Ronchetti","sequence":"additional","affiliation":[{"name":"UOSD SAFU Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6702-3889","authenticated-orcid":false,"given":"Ahlem","family":"Blel","sequence":"additional","affiliation":[{"name":"Pathology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-2917","authenticated-orcid":false,"given":"Marouene","family":"Chakroun","sequence":"additional","affiliation":[{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 Avril 1938, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9226-610X","authenticated-orcid":false,"given":"Seif","family":"Mokadem","sequence":"additional","affiliation":[{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 Avril 1938, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-5403","authenticated-orcid":false,"given":"Zeineb","family":"Naimi","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Salah Azaiez Institute, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2919-1173","authenticated-orcid":false,"given":"Mohamed Ali","family":"Bedoui","sequence":"additional","affiliation":[{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 Avril 1938, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1492-9799","authenticated-orcid":false,"given":"Linda","family":"Bel Haj Kacem","sequence":"additional","affiliation":[{"name":"Pathology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3418-1749","authenticated-orcid":false,"given":"Khedija","family":"Meddeb","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Salah Azaiez Institute, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0366-4630","authenticated-orcid":false,"given":"Soumaya","family":"Rammeh","sequence":"additional","affiliation":[{"name":"Pathology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Riadh","family":"Ben Slama","sequence":"additional","affiliation":[{"name":"Urology Department, Charles Nicolle Hospital, Faculty of Medicine, University of Tunis El Manar, Boulevard 9 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