Circular RNAs and SIRT1 in post-transcriptional regulation and human disease
Year: 2026
Type: article
Abstract: Circular RNAs (circRNAs) have emerged as stable post-transcriptional regulators that influence gene expression, cellular adaptation, and disease pathogenesis through mechanisms including microRNA (miRNA) interaction, RNA-binding protein modulation, and signaling-network regulation. Generated through the back-splicing process that produce covalently closed RNA loops, circRNAs exhibit remarkable stability, evolutionary conservation, and tissue-specific expression patterns, enabling them to function as miRNA sponges, protein scaffolds, transcriptional modulators, and, in some cases, translational templates. Increasing evidence indicates that dysregulated circRNA expression contributes to a broad spectrum of human diseases, highlighting their diagnostic and therapeutic potential. Among the molecular pathways influenced by circRNAs, Sirtuin 1 (SIRT1), an NAD + -dependent deacetylase and a modulator of metabolic homeostasis, stress adaptation, inflammation, autophagy, and aging, has emerged as a particularly important target. Recent studies have revealed that circRNAs regulate SIRT1 through complex post-transcriptional and signaling networks, thereby influencing cellular fate decisions in both malignant and non-malignant disorders. Importantly, the biological consequences of circRNA-mediated SIRT1 modulation appear highly context-dependent, with protective or pathogenic effects varying according to tissue type, metabolic state, and disease stage. In this review, we provide a comprehensive and integrative discussion of the circRNA-SIRT1 regulatory axes across diverse pathological conditions, from common metabolic disorders to life-threatening cancers. Beyond summarizing current evidence, we propose the circRNA-SIRT1 network as a context-dependent post-transcriptional regulatory network linking non-coding RNA (ncRNA) biology to immunometabolic and stress-response pathways. We further discuss emerging translational opportunities and circRNA-targeted therapeutics, emphasizing the potential of this regulatory axis as a promising platform for precision diagnostics and disease-specific therapeutic interventions.
Institutions: Shiraz University of Medical Sciences, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University, Shahid Beheshti University of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Lorestan University of Medical Sciences, Mazandaran University of Medical Sciences, Shiraz University, Children's Hospital Research Institute of Manitoba, Akademia Śląska, Research Institute in Oncology and Hematology, University of Manitoba
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,010
OpenAlex ID: W7208838751