{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:22:40Z","timestamp":1786116160974,"version":"build-2736575974"},"reference-count":226,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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>\n                    Cancer stem cells (CSCs) play a pivotal role in tumor initiation, progression, and therapy resistance. Emerging evidence suggests that non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), intricately regulate CSC properties. This article reviews current knowledge on the intricate interplay between ncRNAs, genetic and epigenetic factors having role in cancer stemness and associated phenotypes. We have also identified key stemness- and EMT-associated genes, including\n                    <jats:italic>OCT4<\/jats:italic>\n                    ,\n                    <jats:italic>SOX2<\/jats:italic>\n                    ,\n                    <jats:italic>NANOG<\/jats:italic>\n                    ,\n                    <jats:italic>KLF4<\/jats:italic>\n                    ,\n                    <jats:italic>CD44<\/jats:italic>\n                    ,\n                    <jats:italic>ALDH1A1<\/jats:italic>\n                    ,\n                    <jats:italic>BMI1<\/jats:italic>\n                    ,\n                    <jats:italic>ZEB1<\/jats:italic>\n                    ,\n                    <jats:italic>ZEB2<\/jats:italic>\n                    ,\n                    <jats:italic>SNAIL<\/jats:italic>\n                    ,\n                    <jats:italic>SLUG<\/jats:italic>\n                    , and\n                    <jats:italic>TWIST1<\/jats:italic>\n                    that are regulated by ncRNAs in different cancer types. Additionally, we have described how ncRNA-mediated regulation of these genes influences major signaling pathways, including Wnt\/\u03b2-catenin, Notch, Hedgehog, PI3K\/AKT\/mTOR, JAK\/STAT, NF-\u03baB, Hippo\/YAP, and TGF-\u03b2 signaling. The mir-21, miR-34, miR-200, and let-7 families target self-renewal and epithelial-to-mesenchymal transition while lncRNAs like H19, HOTAIR, and MALAT1 remodel the regulatory and epigenetic landscape of cancer stem cells. Understanding the interplay between ncRNAs and CSCs offers new insights into potential targeted therapies for combating aggressive and therapy-resistant cancers. Additionally, combining ncRNA interventions with conventional modalities such as chemotherapy, epigenetic drugs along with the advance nanotechnology-based drug delivery systems could result into synergistic outcomes. However, delivery, efficacy, and safety challenges remain. Overall, the ncRNA-cancer stemness interplay warrants therapeutic advancements and clinical translation towards a promising treatment personalization.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1870002","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T07:46:17Z","timestamp":1786002377000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unravelling the nexus of non-coding RNAs in cancer stemness and therapeutic drug resistance"],"prefix":"10.3389","volume":"14","author":[{"given":"Song","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First College of Clinical Medical Sciences, China Three Gorges University","place":["Yichang, China"]},{"name":"Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tikam Chand","family":"Dakal","sequence":"additional","affiliation":[{"name":"Genome and Computational Biology Lab, Department of Biotechnology, Mohanlal Sukhadia University","place":["Udaipur, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Centre for Genetic Disorders, Institute of Science, Banaras Hindu University","place":["Varanasi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip Kumar","family":"Arya","sequence":"additional","affiliation":[{"name":"University School of Pharmaceutical Sciences, Rayat Bahra Professional University","place":["Punjab, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Gogoi","sequence":"additional","affiliation":[{"name":"Mizoram University","place":["Mizoram, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics","place":["Bangalore, India"]},{"name":"Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo G. 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