LncRNAs and the Cancer Epitranscriptome: Mechanisms and Therapeutic Potential

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the cancer epitranscriptome, orchestrating post-transcriptional gene regulation through dynamic interactions with RNA-modifying enzymes and RNA-binding proteins. Acting as molecular guides, scaffolds, decoys, and organizational hubs, lncRNAs regulate the deposition, removal, and interpretation of epitranscriptomic marks, including N6-methyladenosine (m6A), 5-methylcytosine, pseudouridine, and adenosine-to-inosine editing. Through these interactions, lncRNAs influence RNA stability, splicing, translation, localization, and degradation, thereby shaping oncogenic programs that drive proliferation, metabolic reprogramming, stemness, epithelial-mesenchymal transition, metastasis, immune evasion, and therapeutic resistance. Conversely, epitranscriptomic modifications regulate lncRNA abundance, structure, localization, and function, establishing reciprocal regulatory circuits that sustain adaptive cancer phenotypes. This review examines the bidirectional interplay between lncRNAs and the epitranscriptomic machinery, highlights emerging principles of epigenome-epitranscriptome integration, feedback regulation, and spatial organization, and explores their implications for cancer progression and therapeutic response. Understanding these interconnected regulatory networks may facilitate the development of novel biomarkers and precision therapeutic strategies targeting lncRNA-epitranscriptome signaling axes in cancer.