Dynamic modifications of circular RNAs drive oncogenesis

Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs that regulate the progression of multiple cancers. Recent studies have revealed the presence of several post-transcriptional modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytidine (ac4C), and N7-methylguanosine (m7G) on circRNAs. This review synthesizes the results of articles retrieved through systematic searches of PubMed and Web of science databases, mainly focusing on circRNA modifications in cancers. These modifications affect the biogenesis, metabolism, stability, and function of circRNAs in cancers, highlighting the critical roles of circRNAs modifications in cancers. Moreover, circRNAs crosstalk with epigenetic modifications of mRNA across various cancers, offering new perspectives for cancer therapy. Innovations in detection techniques, such as anti-modifying antibodies and mass spectrometry, have improved the identification and sensitivity of epigenetically modified circRNAs. Emerging technologies including artificial intelligence (AI)-based bioinformatics algorithms will accelerate the development of RNA epigenetic modifications-based precision therapies. Herein, we summarize a range of epigenetically modified circRNAs and their future research directions. We hope to develop clinical protocols that targeting circRNAs modification for the treatment of refractory malignancies.