非编码RNA对程序性细胞死亡的调控及其在癌症化疗耐药中的意义

Non-coding RNAs regulating programmed cell death and its implications in cancer chemotherapy resistance.

作者信息

Chen Meijun, Zhao Peng, Chou Jinjiang, Zhou Lianghong, Feng Zili, Hao Xiaojiang, Song Hui, Yang Jue

机构信息

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang 550014, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China.

Department of Cell and Molecular Biology, Karolinska Institutet, Solnavägen 9, Stockholm 17165, Sweden.

出版信息

Int J Biol Macromol. 2025 Jul;318(Pt 2):144888. doi: 10.1016/j.ijbiomac.2025.144888. Epub 2025 Jun 6.

Abstract

Non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), tRNA-derived small RNAs (tsRNAs), and small nucleolar RNAs (snoRNAs) -have emerged as master regulators of cancer biology. Beyond their established roles as diagnostic and prognostic biomarkers, aberrant ncRNAs expression intricately modulates programmed cell death (PCD) processes such as apoptosis, autophagy, ferroptosis, and pyroptosis, thereby shaping tumor responses to chemotherapy. This review presents a unified framework that links six classes of ncRNAs to the four different modalities of PCD modalities in the context of chemoresistance. We systematically dissect the molecular circuits through which ncRNAs influence caspase activation, autophagic flux, lipid peroxidation, and inflammasome assembly, and we highlight how these interactions underpin drug resistance across diverse cancer types. Finally, we evaluate the therapeutic promise of targeting ncRNAs-PCD axes, discuss delivery and specificity challenges, and propose strategic solutions to accelerate clinical translation. This synthesis offers novel mechanistic insights and actionable perspectives for overcoming chemotherapy resistance in cancer management.

摘要

非编码RNA(ncRNAs)——包括微小RNA(miRNAs)、长链非编码RNA(lncRNAs)、环状RNA(circRNAs)、PIWI相互作用RNA(piRNAs)、tRNA衍生的小RNA(tsRNAs)和小核仁RNA(snoRNAs)——已成为癌症生物学的主要调节因子。除了作为诊断和预后生物标志物的既定作用外,异常的ncRNAs表达还复杂地调节程序性细胞死亡(PCD)过程,如凋亡、自噬、铁死亡和焦亡,从而塑造肿瘤对化疗的反应。本综述提出了一个统一的框架,将六类ncRNAs与化疗耐药背景下四种不同的PCD模式联系起来。我们系统地剖析了ncRNAs影响半胱天冬酶激活、自噬通量、脂质过氧化和炎性小体组装的分子途径,并强调了这些相互作用如何在不同癌症类型中支持耐药性。最后,我们评估了靶向ncRNAs-PCD轴的治疗前景,讨论了递送和特异性挑战,并提出了加速临床转化的战略解决方案。这一综合分析为克服癌症治疗中的化疗耐药性提供了新的机制见解和可行的观点。

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