非编码RNA调控铜死亡相关基因在消化道肿瘤中的研究进展  

Noncoding RNAs Regulate Cuproptosis-related Genes in Digestive Tract Tumors:Research Progress

作　　者：杜予心 王小平 DU Yuxin;WANG Xiaoping(Key Laboratory of High Altitude Hypoxia Environment and Life Health,School of Medicine,Xizang Minzu University,Xianyang 712082,China)

机构地区：[1]西藏民族大学医学院高原低氧环境与生命健康实验室,陕西咸阳712082

出　　处：《中山大学学报(医学科学版)》2025年第2期230-237,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(82460515);中央引导地方科技发展资金项目(LSKJ202447);咸阳市科技计划重点研发项目(L2024-ZDYF-SF-0025)。

摘　　要：铜是人体中的微量元素,与各种信号通路和肿瘤相关生物行为密切相关,但浓度超过稳态机制维持的阈值就会变得有毒,引发细胞死亡。铜死亡是一种全新的细胞死亡方式,不同于所有其他已知的细胞死亡途径,通过铜与三羧酸循环的硫辛酰化组分直接结合而发生,这导致硫辛酰化蛋白质聚集和铁硫簇蛋白丢失,引发蛋白毒性应激最终导致细胞死亡,在消化道肿瘤的发生、发展和预后中发挥作用。长链非编码RNA(lncRNA)、微小RNA(miRNA)和环状RNA(circRNA)等非编码RNA(ncRNAs)基于ceRNA机制直接或间接调控消化道肿瘤铜死亡相关基因(FDX1、LIPT1、LIAS、DLD、DLAT、PDHA1、PDHB、MTF1、GLS、CDKN2A)的表达,进而诱导铜离子积聚,通过驱动氧化应激反应、蛋白质脂酰化、泛素-蛋白酶体系统多种机制,抑制消化道肿瘤细胞的发生发展。ncRNAs通过调控铜死亡相关基因的表达影响肿瘤细胞的发生发展为临床精准靶向治疗消化道肿瘤提供了新的思路。本文通过介绍铜死亡,梳理铜死亡的多种调控机制,ncRNAs和其作用,综述近年来参与调控食管癌、胃癌、肝癌、结直肠癌和胰腺癌等消化道肿瘤铜死亡的ncRNAs及其分子作用机制,并提出临床方面展望,以期为消化道肿瘤的诊治提供理论依据。Copper is a trace element in the human body and is closely related to various signaling pathways and tumor-related biological behaviors.However,when its concentration exceeds the threshold maintained by homeostatic mechanisms,it becomes toxic and triggers cell death.Cuproptosis is a novel form of cell death,distinct from all other known cell death pathways.It occurs through the direct binding of copper to the lipoic acid components of the tricarboxylic acid cycle,leading to the aggregation of lipoic-acylated proteins and the loss of iron-sulfur cluster proteins.This triggers protein toxicity stress,ultimately resulting in cell death.Cuproptosis plays a role in the occurrence,development,and prognosis of digestive tract tumors.Noncoding RNAs(ncRNAs)such as long non-coding RNA(lncRNA),micro RNA(miRNA)and circular RNA(circRNA)directly or indirectly regulate the expression of cuproptosis-related genes(FDX1,LIPT1,LIAS,DLD,DLAT,PDHA1,PDHB,MTF1,GLS and CDKN2A)in digestive tract tumors based on ceRNA mechanism,thereby inducing copper ion accumulation,driving oxidative stress response,protein fatty acylation and ubiquitin-proteasome system,inhibiting the occurrence and development of digestive tract tumor cells.NcRNAs’implication in the genesis of tumor cells via regulating cuproptosis-related genes provides a new insight into precision targeted therapy for tumors.This article introduces cuproptosis,outlines the various regulatory mechanisms of cuproptosis,and provides an overview of ncRNAs and their roles.It reviews recent research on ncRNAs involved in regulating cuproptosis in digestive tract tumors such as esophageal squamous cell carcinoma,gastric cancer,hepatocellular carcinoma,colorectal carcinoma,pancreatic cancer,along with their molecular mechanisms.The article also presents clinical perspectives,aiming to provide a theoretical basis for the diagnosis and treatment of digestive tract tumors.

关 键 词：铜死亡 非编码RNA 消化道肿瘤 信号轴 综述 

分 类 号：R735[医药卫生—肿瘤]