circRNF13, a novel N(6)-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability

BACKGROUND: Circular RNAs (circRNAs) and N(6)-methyladenosine (m(6)A) have been shown to play an increasingly critical role in the development of different cancers. However, there is limited evidence on how circRNAs and m(6)A interact to affect the radiosensitivity of cervical cancer (CC). This study provides a mechanistic understanding of the novel m(6)A-regulated circRNF13 in enhancing radioresistance in CC. METHODS: Differentially expressed circRNAs were identified from radiosensitive and radioresistant CC tissues. Meanwhile, these circRNAs were subjected to methylated RNA immunoprecipitation (Me-RIP). Finally, the effects of these circRNAs on radiosensitivity were characterized. RESULTS: CircRNF13 was poorly expressed in CC patients that were sensitive to concurrent radiochemotherapy. Experiments conducted both in vitro and in vivo confirmed that the knockdown of circRNF13 potentiated the radiosensitivity of CC cells. Further mechanistic studies revealed that METTL3/YTHDF2 promoted the degradation of circRNF13 and subsequently affected the stability of CXC motif chemokine ligand 1 (CXCL1), ultimately enhancing the radiosensitivity of CC cells. CONCLUSION: This study identified circRNF13 as a novel m(6)A-modified circRNA and validated the METTL3/YTHDF2/circRNF13/CXCL1 axis as a potential target for CC radiotherapy.