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The role of long non-coding RNAs in NK cell biology and diseases

Review Articles

The role of long non-coding RNAs in NK cell biology and diseases

Zhang Dan
Wei Siqiao
Wei Qianqiu
Lin Zhansong
Sun Xiaoming
Genes & Diseases第13卷, 第3期纸质出版 2026-05-01在线发表 2025-08-25
400

Long non-coding RNAs (lncRNAs) are pivotal regulators of gene expression, increasingly recognized for their roles in immune responses and disease progression. Natural killer (NK) cells, essential cytotoxic lymphocytes of the innate immune system, orchestrate immune responses through cytokine secretion and direct cytotoxicity. This review elucidates the immunomodulatory functions of lncRNAs in NK cell biology and their implications in pathological conditions. LncRNAs intricately govern key NK cell processes, including development, differentiation, activation, recruitment, cytotoxic function, and immune infiltration within the tumor microenvironment. These regulatory effects are mediated through diverse mechanisms, such as transcriptional control of effector molecules, miRNA sponging, metabolic reprogramming, protein ubiquitination, and epigenetic modifications. Focusing on NK cell infiltration in tumors, we classify lncRNAs into mechanistically defined and uncharacterized groups, highlighting their roles in tumor-associated competing endogenous RNA (ceRNA) networks, epigenetic regulation, and cell death pathways. By integrating these perspectives, this review enhances our understanding of lncRNA-mediated immune regulation and underscores their potential as therapeutic targets for diseases involving NK cell dysfunction.

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Cytotoxic activityInnate immune cellsLong non-coding RNAsMultiple diseasesNK cell