Abstract
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 (o(8)G) 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 (CaCO(2) cells) were constructed by knocking down the ADAR1 gene. RNA immunoprecipitation sequencing was used to identify the o(8)G peaks on messenger RNA (mRNA) of normal CaCO(2) cells and senescent CaCO(2) cells, and the distribution characteristics of mRNA o(8)G modification were identified. Further bioinformatics analysis of the sequencing data was performed to preliminarily elucidate the potential function of the o(8)G-modified mRNA. RESULTS: There were significant differences in mRNA o(8)G modification distribution between normal and senescent CaCO(2) cells. It is suggested that o(8)G 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 o(8)G 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 o(8)G 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 o(8)G modification between normal CaCO(2) cells and senescent CaCO(2) cells. Our study established the link between o(8)G 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.