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

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.