作为与结直肠癌生存结果相关的细胞衰老生物标志物的RNA假尿苷修饰的转录组学特征

Transcriptomic profile of RNA pseudouridine modification as a biomarker for cellular senescence associated with survival outcomes in colorectal cancer.

作者信息

Gan Yingguo, Yuan Ze, Weng Jingrong, Huang Mingzhe, Li Tuoyang, Wu Yuanhui, Lin Kaixin, Han Junyi, Li Xuan, Liu Haotian, Wan Zixiao, Li Ziming, Chen Zhenghua, Cui Ji, Luo Yanxin, Huang Meijin, Yu Huichuan, Lin Jinxin

机构信息

Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China.

出版信息

BMC Biol. 2025 Feb 27;23(1):61. doi: 10.1186/s12915-025-02170-6.

DOI:10.1186/s12915-025-02170-6

PMID:40016751

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11866714/

Abstract

BACKGROUND

Colorectal cancer (CRC) is considered as an age-related disease, and cellular senescence (CS) plays a crucial role in cancer development and progression. Previous studies have shown the role of epigenetic changes in aging and cancer development, but the role of RNA pseudouridine (Ψ) modification in aging and cancer remains to be explored.

RESULTS

Using bulk RNA sequencing, CRC cells with low Ψ writers expression levels have higher CS levels. We developed the Psi Score for assessing the transcriptomic profile of RNA Ψ modification regulation and found that the Psi Score correlates with CS. Furthermore, Psi-related senescence may be mediated by mTOR, TGF-β, TNF-α, and inflammatory response signaling pathways. Meanwhile, Psi Score could predict the anti-cancer treatment outcomes of anti-aging interventions and could be used to predict the response to immunotherapy.

CONCLUSIONS

Overall, these findings reveal that RNA Ψ modification connected aging and cancer and provided novel insights into biomarker-guided cancer regimens.

摘要

背景

结直肠癌（CRC）被认为是一种与年龄相关的疾病，细胞衰老（CS）在癌症的发生和发展中起着关键作用。先前的研究已经表明表观遗传变化在衰老和癌症发展中的作用，但RNA假尿苷（Ψ）修饰在衰老和癌症中的作用仍有待探索。

结果

使用批量RNA测序，低Ψ写入器表达水平的CRC细胞具有更高的CS水平。我们开发了Psi评分来评估RNA Ψ修饰调控的转录组谱，发现Psi评分与CS相关。此外，Psi相关的衰老可能由mTOR、TGF-β、TNF-α和炎症反应信号通路介导。同时，Psi评分可以预测抗衰老干预措施的抗癌治疗结果，并可用于预测对免疫治疗的反应。