{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:07:49Z","timestamp":1784700469993,"version":"3.55.0"},"reference-count":146,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Cancer remains a major global health burden, with its incidence and mortality rates persistently high despite advances in treatment. Despite therapeutic innovations, malignant tumors continue to pose a formidable challenge to global health. Against this backdrop, the crosstalk between long non-coding RNAs (lncRNAs) and the Notch signaling pathway has emerged as a pivotal driver of tumorigenesis and progression. However, the complex regulatory network and a comprehensive mechanistic framework of this axis await systematic elucidation. This review systematically consolidates recent advances in understanding how lncRNAs precisely modulate Notch pathway activity through diverse mechanisms, including acting as competing endogenous RNAs, direct protein binding, epigenetic regulation, and exosome-mediated intercellular communication. The discussion encompasses various malignancies, spanning the digestive, respiratory, urogenital, nervous, and hematologic systems. The lncRNA-Notch regulatory axis is identified as a ubiquitous and functionally central oncogenic network. It orchestrates critical malignant phenotypes\u2014such as such as stemness maintenance, epithelial-mesenchymal transition, metabolic shifts, drug resistance, and immune evasion\u2014through intricate bidirectional crosstalk. Functional studies confirm that targeting key nodes of this axis can effectively reverse drug resistance and suppress tumor growth. Although challenges remain in its clinical translation, future research integrating single-cell multi-omics, nanotechnology, and other innovative strategies will undoubtedly open new avenues for precision diagnosis and cancer therapy.<\/jats:p>","DOI":"10.3389\/fcell.2026.1903203","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:56:36Z","timestamp":1784699796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic insights into the lncRNA-Notch signaling axis in tumors"],"prefix":"10.3389","volume":"14","author":[{"given":"Qingmiao","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwu","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiya","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1038\/s41467-026-71569-8","article-title":"SETDB1 and HUSH modulate Xist RNA levels during establishment of X chromosome inactivation","volume":"17","author":"Almeida","year":"2026","journal-title":"Nat. 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