{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:59:35Z","timestamp":1787237975399,"version":"build-2736575974"},"reference-count":121,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Renal cell carcinoma (RCC) represents the most frequent kidney malignancy and remains a major clinical challenge due to its often silent onset, high metastatic potential, and limited responsiveness to conventional chemotherapy. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of RCC tumorigenesis, progression, and therapy resistance. Rather than providing a purely descriptive overview, this review focuses on emerging mechanistic paradigms through which ncRNAs actively shape tumor behavior and therapeutic response in RCC. This review summarizes current knowledge on the biological and clinical relevance of ncRNAs in RCC, highlighting their dual roles as oncogenic drivers or tumor suppressors through the modulation of pathways involved in proliferation, apoptosis, angiogenesis, invasion, immune evasion, metabolic reprogramming, and ferroptosis. Particular emphasis is placed on mechanistically defined ncRNA regulatory axes controlling ferroptosis, autophagy, metabolic reprogramming, and immune escape, as well as on ncRNA-mediated intercellular communication via extracellular vesicles, which promotes the dissemination of resistance to targeted therapies. The review also addresses ncRNA-based diagnostic and prognostic applications, including miRNA signatures capable of discriminating RCC subtypes and circulating ncRNAs as minimally invasive biomarkers. Moreover, the manuscript discusses ncRNA-mediated mechanisms of resistance to targeted therapies such as sunitinib, sorafenib, and axitinib, emphasizing regulatory networks involving miRNA targets, lncRNA\u2013miRNA sponging, RNA-binding proteins, extracellular vesicle transfer, and epigenetic modulation. Emerging therapeutic opportunities are also addressed, including strategies aimed at inhibiting oncogenic ncRNAs or restoring tumor-suppressive ncRNAs to enhance drug sensitivity and improve patient stratification.<\/jats:p>","DOI":"10.3390\/ncrna12020008","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:05:16Z","timestamp":1772211916000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Short and Long Non-Coding RNAs in Renal Cell Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Monia","family":"Cecati","sequence":"first","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3941-0341","authenticated-orcid":false,"given":"Valentina","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9943-3908","authenticated-orcid":false,"given":"Valentina","family":"Schiavoni","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Barrasso","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Pompei","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-0270","authenticated-orcid":false,"given":"Daniela","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Bonci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-741X","authenticated-orcid":false,"given":"Stefania","family":"Fumarola","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-1415","authenticated-orcid":false,"given":"Andrea","family":"Ballini","sequence":"additional","affiliation":[{"name":"Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3879-8647","authenticated-orcid":false,"given":"Davide","family":"Sartini","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-2734","authenticated-orcid":false,"given":"Roberto","family":"Campagna","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2147\/JMDH.S480747","article-title":"Prediction of Distant Metastasis of Renal Cell Carcinoma Based on Interpretable Machine Learning: A Multicenter Retrospective Study","volume":"18","author":"Dong","year":"2025","journal-title":"J. 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