Landscape of N(4)- acetylcytidine modified genes in triple-negative breast cancer Revealing the potential markers of N(4)-acetylcytidine through acRIP-seq in triple-negative breast cancer

Background: Triple-negative breast cancer (TNBC) still lacks effective treatments, and understanding the causes of its tumorigenesis and tumor progression is helpful for prognostic evaluation. N(4)-acetylcytidine (ac4C), an epigenetic modification of RNA, whose regulatory mechanism is still unclear in TNBC tumors may provide a new perspective for understanding the development of TNBC. Methods: Two pairs of TNBC patient tissues were sequenced at the genome level using acRIP-seq technology, and differential ac4C genes were identified by Robust Rank Aggregation (RRA). Then, by integrating genome-wide lncRNA expression profiles in TCGA, we constructed a co-expression network containing 180 ac4C genes and mined 1080 lncRNA gene relationship pairs. And use cox regression analysis to screen genes associated with prognosis. Additionally, drug sensitivity was predicted using a drug target network of differential ac4C genes. Results: We screened a total of 180 differential ac4c genes, of which 6 genes were significantly associated with prognosis. In addition, we screened out three lncRNAs interacting with prognostic risk genes, and the corresponding interaction pairs were "LINC01614-COL3A1", "OIP5-AS1-USP8" and "RP5-908M14.9-TRIR". Significant ac4C genes COL3A, USP8 and TRIR1 were accurately predicted with the sensitivity of Doxorubicin and Paclitaxel, the main chemotherapy drugs in TNBC. Conclusions: This study suggests that RNA ac4C acetylation may be a potential marker of prognosis and drug sensitivity/target through the involvement of lncRNA. These results will be used as a guide for experiments.