Revealing the Potential Markers of N(4)-Acetylcytidine through acRIP-seq in Triple-Negative Breast Cancer

Abstract

Understanding the causes of tumorigenesis and progression in triple-receptor negative breast cancer (TNBC) can help the design of novel and personalized therapies and prognostic assessments. Abnormal RNA modification is a recently discovered process in TNBC development. TNBC samples from The Cancer Genome Atlas database were categorized according to the expression level of NAT10, which drives acetylation of cytidine in RNA to N(4)-acetylcytidine (ac4C) and affects mRNA stability. A total of 703 differentially expressed long non-coding RNAs (lncRNAs) were found between high- and low-expressed NAT10 groups in TNBC. Twenty of these lncRNAs were significantly associated with prognosis. Two breast cancer tissues and their paired normal tissues were sequenced at the whole genome level using acetylated RNA immunoprecipitation sequencing (acRIP-seq) technology to identify acetylation features in TNBC, and 180 genes were significantly differentially ac4c acetylated in patients. We also analyzed the genome-wide lncRNA expression profile and constructed a co-expression network, containing 116 ac4C genes and 1080 lncRNAs. Three of these lncRNAs were prognostic risk lncRNAs affected by NAT10 and contained in the network. The corresponding reciprocal pairs were “LINC01614-COL3A1”, “OIP5-AS1-USP8”, and “RP5-908M14.9-TRIR”. These results indicate that RNA ac4c acetylation involves lncRNAs and affects the tumor process and prognosis of TNBC. This will aid the prediction of drug targets and drug sensitivity.

STM-ac4C: a hybrid model for identification of N4-acetylcytidine (ac4C) in human mRNA based on selective kernel convolution, temporal convolutional network, and multi-head self-attention

“…We used the high-quality dataset constructed by Su et al to evaluate our model. The dataset was derived from the experimental data of Arango et al ( Arango et al, 2018 ), which identified 4,250 ac4C peaks using the acRIP-seq method ( Zhang X. et al, 2022 ). Su et al ( Su et al, 2023 ) extracted sequences of 100 nt up and down as positive samples to create a reliable dataset, starting from the cytosine near each ac4C peak.…”

Revealing the pharmacological effects of Remodelin against osteosarcoma based on network pharmacology, acRIP-seq and experimental validation

“…NAT10, the sole protein encompassing both an N-acetyltransferase structural domain and a nucleotide-binding region, is regarded as an ac4C ‘writer’ protein responsible for governing RNA modification mechanisms. In cancer, NAT10 is usually expressed at high levels to maintain mRNA acetylation, which in turn promotes mRNA stability and translation 10 . Remodelin, as a novel small molecule, has been shown to reduce NAT10 activity 11 , thus preventing mRNA acetylation, and has been shown to be an effective treatment for various types of tumors 2 .…”

Recent advances in the potential role of RNA N4-acetylcytidine in cancer progression

“…Zhang et al [ 106 ] collected TNBC tissue samples and classified them according to NAT10 expression to understand the role of ac 4 C modification in TNBC progression and help design new personalized treatment plans and prognostic assessment. They found 703 lncRNAs differentially expressed between the high and low NAT10 expression groups, of which 20 lncRNAs were associated with disease prognosis.…”