lncRNA EPB41L4A-AS1: A promising therapeutic target for aging and age-related diseases.

IF 5.1 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development Pub Date : 2025-10-07 DOI:10.1016/j.mad.2025.112118

Minghui Li, Tianzi Li, Xufei Zhang, Kun Li, Ziqiang Wang

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引用次数: 0

Abstract

Aging is a natural biological process characterized by progressive cellular and functional decline, significantly increasing susceptibility to age-related diseases. Long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators of cellular processes implicated in aging and age-related diseases. Among these, lncRNA erythrocyte membrane protein band 4.1 like 4A antisense RNA 1 (EPB41L4A-AS1) has emerged as a key player with significant dysregulation across diverse age-related diseases including cancer, Alzheimer's disease (AD), and type 2 diabetes mellitus (T2DM). This review synthesizes current evidence showing that EPB41L4A-AS1 functions primarily as a tumor suppressor in many cancers, regulates neuronal autophagy and energy metabolism in AD, and modulates inflammatory and metabolic pathways in T2DM. Mechanistically, EPB41L4A-AS1 exerts its effects-via miRNA sponging, regulating key signaling pathways (NF-κB, Rho/ROCK), influencing histone modifications, and modulating cellular metabolism (glycolysis, glutaminolysis, NAD+/ATP synthesis). The compelling evidence positions EPB41L4A-AS1 as a promising, multi-faceted therapeutic target for mitigating the burden of age-related diseases.

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lncRNA EPB41L4A-AS1：一个有希望的治疗衰老和年龄相关疾病的靶点

衰老是一个自然的生物学过程，其特征是细胞和功能的进行性衰退，显著增加对年龄相关疾病的易感性。长链非编码rna （lncRNAs）越来越被认为是涉及衰老和年龄相关疾病的细胞过程的关键调节因子。其中，lncRNA红细胞膜蛋白带4.1如4A反义RNA 1 （EPB41L4A-AS1）已成为多种年龄相关疾病（包括癌症、阿尔茨海默病（AD）和2型糖尿病（T2DM））中显著失调的关键参与者。本综述综合了目前的证据，表明EPB41L4A-AS1在许多癌症中主要作为肿瘤抑制因子，调节AD中的神经元自噬和能量代谢，并调节T2DM中的炎症和代谢途径。在机制上，EPB41L4A-AS1通过miRNA海绵作用发挥作用，调节关键信号通路（NF-κB, Rho/ROCK），影响组蛋白修饰，调节细胞代谢（糖酵解，谷氨酰胺解，NAD+/ATP合成）。令人信服的证据表明，EPB41L4A-AS1是一个有希望的、多方面的治疗靶点，可以减轻年龄相关疾病的负担。

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来源期刊

Mechanisms of Ageing and Development 医学-老年医学

CiteScore

11.10

自引率

1.90%

发文量

审稿时长

32 days

期刊介绍： Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.