Overview of distinct 8-oxoguanine profiles of messenger RNA in normal and senescent cancer cells

BACKGROUND: Cellular senescence plays a key role in the development of cancer, but the underlying mechanisms are unknown. Recently, several recent studies have shown that RNA methylation is closely related to cancer cell aging. 8-Oxoguanine (o⁸G) is an important and widely distributed methylation modification whose role in cancer cell senescence is far from elucidated. METHODS: In this study, senescent cancer cell models (CaCO₂ cells) were constructed by knocking down the ADAR1 gene. RNA immunoprecipitation sequencing was used to identify the o⁸G peaks on messenger RNA (mRNA) of normal CaCO₂ cells and senescent CaCO₂ cells, and the distribution characteristics of mRNA o⁸G modification were identified. Further bioinformatics analysis of the sequencing data was performed to preliminarily elucidate the potential function of the o⁸G-modified mRNA. RESULTS: There were significant differences in mRNA o⁸G modification distribution between normal and senescent CaCO₂ cells. It is suggested that o⁸G modification may play a key role in inducing cancer cells or promoting cancer cell senescence. Gene ontology (GO) enrichment analysis showed that the mRNAs modified by o⁸G were enriched in Cellular component organization or biogenesis, Focal adhesion, and RNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the genes modified by o⁸G are concentrated in Focal adhesion signaling pathway, Small cell lung cancer signaling pathway and Proteoglycans in cancer signaling pathway. CONCLUSION: This study preliminarily revealed the different distribution patterns of o⁸G modification between normal CaCO₂ cells and senescent CaCO₂ cells. Our study established the link between o⁸G modification and cancer cell senescence, which provides a new insight into the mechanism of cancer cell senescence and a potential therapeutic target for subsequent cancer treatment.