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5-Methylcytosine (m5C) modification is an important type of RNA methylation. Diverse noncoding RNAs can undergo m5C modification and play important roles in tumour development, but circRNA m5C modifications have not been fully revealed in tumours. Here, circFAM190B, which was significantly overexpressed in lung cancer cells and tissues, was identified by constructing a differential expression profile of m5C-modified circRNAs. circFAM190B was found to be associated with lung cancer stage and prognosis. Moreover, we proposed the novel hypothesis that NSUN2 can mediate circFAM190B m5C modification and enhance circFAM190B stability in an m5C-dependent manner. We also clarified the biological function of circFAM190B in significantly promoting the development of lung cancer. Mechanistically, circFAM190B targets SFN and regulates its ubiquitination, thereby inhibiting cellular autophagy through the SFN/mTOR/ULK1 pathway and ultimately promoting lung cancer development. This study reveals the existence of m5C modification of circRNAs, and circRNAs modified by m5C can play important roles in the development of lung cancer, which provides a new theoretical basis for elucidating the molecular mechanism of lung cancer development. • circRNA can undergo m5C modification. NSUN2 can act as a writer of circFAM190B and thus enhance circFAM190B. • m5C-modified circFAM190B can perform a biological function in promoting non-small cell lung cancer progression by regulating cellular autophagy. • circFAM190B inhibits cellular autophagy via the SFN/mTOR/ULK1 novel signalling pathway.
Chen et al. (Wed,) studied this question.