Dysregulation of lncRNAs in NK cells from breast cancer patients: implications for NK cell functions

Natural killer (NK) cells, a key component of the innate immune system, play a crucial role in detecting and eliminating cancer cells, contributing to cancer immune surveillance. Increasing evidence suggests that NK cell functions are regulated by epigenetic mechanisms, including the influence of long non-coding RNAs (lncRNAs). These lncRNAs, transcripts longer than 200 nucleotides, are emerging as important regulators of gene expression. In this study, we investigated the expression of 84 lncRNAs in NK cells isolated from the peripheral blood of patients with invasive breast cancer. Using lncRNA PCR array profiling, we identified 26 differentially expressed lncRNAs in circulating NK cells isolated from peripheral blood of breast cancer patients, with 10 genes showing significant downregulation and 16 genes showing significant upregulation. Gene ontology (GO) and functional enrichment analysis revealed that among the ten downregulated lncRNAs, four lncRNAs have deposited gene ontology terms and known biological functions. These lncRNAs are PTENP1-AS (fold change 0.27, P = 0.0206), TSIX (fold change 0.05, P = 0.0037), XIST (fold change 0.42, P = 0.007), and CCAT1 (fold change 0.09, P = 0.0191). On the other hand, among the 16 upregulated lncRNAs, five lncRNAs have deposited gene ontology terms and known biological functions. These lncRNAs are GNAS-AS1 (fold change 5.10, P = 0.0104), MEG3 (fold change 46.85, P = 0.0138), CDKN2B-AS1 (fold change 81.80, P = 0.0087), HOTAIR (fold change 6.86, P = 0.0042), and AIRN (fold change 7.97, P = 0.0379). Functional enrichment analysis indicated that the downregulated lncRNAs were mainly involved in biological processes such as chromatin organization, epigenetic regulation of gene expression, and dosage compensation via X chromosome inactivation, while the upregulated lncRNAs were linked to epigenetic regulation, genomic imprinting, and chromatin remodeling. These enrichments were identified using Bonferroni correction with an adjusted P-value < 0.05. Given the biological functions of the dysregulated lncRNAs in NK cells from breast cancer patients, this has the potential to significantly impact the antitumor functionality of NK cells, possibly contributing to the impaired immune surveillance and tumor control commonly observed in breast cancer patients. Understanding the dysregulation of lncRNAs in NK cells may provide critical insights into the mechanisms underlying impaired NK cell function in breast cancer, offering promising approaches for developing immunotherapies aiming at restoring NK cell activity in cancer patients.