MINI REVIEW article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
This article is part of the Research TopicDeciphering molecular mechanisms behind tumor heterogeneity features by using nucleic acid-based technologiesView all 7 articles
Long Noncoding RNAs in tumor stemness: Emerging Mechanisms and Therapeutic Opportunities
Provisionally accepted
- Biochemistry, University of São Paulo, São Paulo, SP, Brazil
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Cancer stem cells (CSCs) constitute a subpopulation of malignant cells with self-renewal and differentiation capabilities that drive tumorigenicity, metabolic adaptability, immune evasion, and therapeutic resistance, key factors contributing to metastasis and poor clinical outcomes. While genetic drivers of tumorigenesis are well-characterized, the epigenetic machinery sustaining the CSC state remains complex. Long noncoding RNAs (lncRNAs) represent a vast yet poorly understood class of regulatory molecules that influence gene expression at epigenetic, transcriptional, and post-transcriptional levels. Emerging evidence indicates that lncRNAs play a crucial role in shaping tumor cell plasticity and stemness-associated phenotypes. In this mini-review, we summarize current findings on how lncRNAs regulate CSC biology. We categorize their mechanisms of action, ranging from chromatin remodeling to the modulation of mRNA and protein stability. Furthermore, we discuss how the advent of high-resolution omics, including bulk tissue, single-cell, and spatial transcriptomics studies, is revolutionizing the identification CSC-associated lncRNAs and contributing to the development of clinically relevant biomarkers. Finally, we explore advanced methodologies for manipulating lncRNA expression, assessing the challenges and opportunities of lncRNA-directed therapeutics as a novel strategy to dismantle tumor plasticity and overcome drug resistance.
Keywords: biomarkers, cancer stem cells, epigenetics, lncRNAs, RNA therapeutics, therapeutic targets, tumor heterogeneity, tumor plasticity
Received: 22 Dec 2025; Accepted: 12 Feb 2026.
Copyright: © 2026 Reis and Bassères. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Eduardo M Reis
Daniela Sanchez Bassères
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