SNORA56-mediated pseudouridylation of 28 S rRNA inhibits ferroptosis and promotes colorectal cancer proliferation by enhancing GCLC translation

作者：Chang Xu, Zhixuan Bian, Xinyue Wang, Na Niu, Li Liu, Yixuan Xiao, Jiabei Zhu, Nan Huang, Yue Zhang, Yan Chen, Qi Wu, Fenyong Sun, Xiaoli Zhu, Qiuhui Pan · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2023 · DOI：10.1186/s13046-023-02906-8 · 被引用次数：30 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Ferroptosis and cancer prognosis

Abstract Background Colorectal cancer (CRC) is one of the most common malignancies and is characterized by reprogrammed metabolism. Ferroptosis, a programmed cell death dependent on iron, has emerged as a promising strategy for CRC treatment. Although small nucleolar RNAs are extensively involved in carcinogenesis, it is unclear if they regulate ferroptosis during CRC pathogenesis. Methods The dysregulated snoRNAs were identified using published sequencing data of CRC tissues. The expression of the candidate snoRNAs, host gene and target gene were assessed by real-time quantitative PCR (RT-qPCR), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and western blots. The biological function of critical molecules was investigated using in vitro and in vivo strategies including Cell Counting Kit-8 (CCK8), colony formation assay, flow cytometry, Fe 2+ /Fe 3+ , GSH/GSSG and the xenograft mice models. The ribosomal activities were determined by polysome profiling and O-propargyl-puromycin (OP-Puro) assay. The proteomics was conducted to clarify the downstream targets and the underlying mechanisms were validated by IHC, Pearson correlation analysis, protein stability and rescue assays. The clinical significance of the snoRNA was explored using the Cox proportional hazard model, receiver operating characteristic (ROC) and survival analysis. Results Here, we investigated the SNORA56, which was elevated in CRC tissues and plasma, and correlated with CRC prognosis. SNO...