Pharmacol Ther. 2026 Sep 25:109128. doi: 10.1016/j.pharmthera.2026.109128. Online ahead of print.
ABSTRACT
Transposable elements (TEs), commonly known as "jumping genes," constitute nearly half of the human genome and are increasingly recognized as important regulators of gene expression, chromatin organization, and immune signaling. Although most TEs are epigenetically silenced under physiological conditions, aging, chronic inflammation, and cancer can induce TE reactivation, leading to genomic instability, innate immune activation, and transcriptional reprogramming. Emerging evidence demonstrates that TEs contribute to immune cell differentiation, enhancer landscape formation, interferon signaling, and inflammatory responses through diverse mechanisms, including the generation of regulatory non-coding RNAs, alternative splicing events, and TE-derived peptides presented by major histocompatibility complex molecules. In addition to their roles in cancer biology, dysregulated TE activities have also been implicated in aging-associated and inflammatory disorders. In this review, we summarize the classification and regulatory functions of TEs, discuss their roles in immune regulation, inflammation and cancer, and examine emerging therapeutic strategies targeting TE-associated pathways in cancer and inflammatory diseases.
PMID:42790755 | DOI:10.1016/j.pharmthera.2026.109128