Circular RNAs as key regulators in cancer hallmarks: New progress and therapeutic opportunities
Bashdar Mahmud Hussen, Snur Rasool Abdullah, Rayan Mazin Jaafar, Mohammed Fatih Rasul, Rouben Aroutiounian, Tigran Harutyunyan, Thomas Liehr, Majid Samsami, Mohammad Taheri
Abstract
Circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, contributing to various cancer hallmarks, including cell proliferation, apoptosis, metastasis, and drug resistance. Defined by their covalently closed loop structure, circRNAs possess unique characteristics like high stability, abundance, and tissue-specific expression. These non-coding RNAs function through mechanisms such as miRNA sponging, interactions with RNA-binding proteins (RBPs), and modulating transcription and splicing. Advances in RNA sequencing and bioinformatics tools have enabled the identification and functional annotation of circRNAs across different cancer types. Clinically, circRNAs demonstrate high specificity and sensitivity in samples, offering potential as diagnostic and prognostic biomarkers. Additionally, therapeutic strategies involving circRNA mimics, inhibitors, and delivery systems are under investigation. However, their precise mechanisms remain unclear, and more clinical evidence is needed regarding their roles in cancer hallmarks. Understanding circRNAs will pave the way for novel diagnostic and therapeutic approaches, potentially improving patient outcomes. The schematic illustration represents the role of several circRNAs in the development of different cancer hallmarks. These ncRNAs have multifaceted roles in promoting tumor proliferation, invasion, metastasis, angiogenesis, evasion of the immune system, enabling replicative immortality, and apoptosis. • CircRNAs play key roles in cancer by regulating processes like cell proliferation, metastasis, and drug resistance. • Their stability, abundance, and tissue-specific expression make circRNAs valuable for cancer diagnosis. • Advances in sequencing tools have helped identify circRNAs as potential targets for cancer therapies.