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Life sciences · Journal article
Annual Review of Pathology Mechanisms of Disease · October 13, 2026
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Ninety-eight percent of the human transcriptome lacks protein-coding potential. A small fraction of this landscape comprises housekeeping noncoding RNAs (ncRNAs) with well-defined functions, whereas the heterogeneous group of regulatory ncRNAs, generated from ∼100,000 loci, acts through diverse mechanisms to control gene expression, chromatin states, RNA processing, and signaling networks. Their recent evolutionary expansion reflects the increasing regulatory complexity of cell and tissue specification programs in higher organisms. In cancer, such programs are co-opted, with fine-tuned regulatory control contributing to the rewiring of molecular networks during transformation, metastasis, and adaptation to therapy. Here, we review the molecular functions of ncRNAs and their involvement in cancer, with emphasis on regulatory classes including microRNAs, long noncoding RNAs, and circular RNAs. We also describe emerging technical innovations that advance their investigation, including genetic tools enabling systematic, context-resolved mapping of ncRNA functions. We conclude by discussing the translational potential of ncRNAs as biomarkers and therapeutic targets.