The Practical Landscape of Cytokine‐Targeted miRNAs to Enhance NK Cell Function in Cancer Immunotherapy: A Bioinformatic Analysis

Abstract

ABSTRACT Introduction Suppression within the tumor microenvironment (TME) hampered natural killer (NK) cells and their role in cancer immunotherapy. This study explores how interleukin (IL) signaling (IL‐12A, IL‐12B, IL‐15, IL‐18) and interferon gamma (IFNG or IFN‐γ) interact with microRNAs to regulate NK cell function in cancer. Methods We identify the targeted microRNAs (miRNAs) for these genes and the key pathways influencing various cancers through comprehensive analyses, including protein–protein interaction networks, protein co‐expression, miRNA targeting prediction, homology, mRNA‐miRNA regulatory networks, gene set enrichment, and signaling pathway analysis. Results Our analysis revealed a significant association between genes encoding interleukins and IFNG with NK cell infiltration across various cancers. Additionally, we identified several miRNAs (hsa‐miR‐590‐3p, hsa‐miR‐340‐5p, hsa‐miR‐495‐3p, hsa‐miR‐5692a, hsa‐miR‐130a‐3p) that potentially regulate NK cell function by targeting these genes. These miRNAs participate in critical pathways essential for NK cell function. Notably, our findings suggest a key role for mRNA‐miRNA co‐regulation in suppressing NK cells within the tumor microenvironment. Conclusion This study highlights the potential of targeting these identified miRNAs as a strategy to enhance NK cell function and improve the efficacy of cancer immunotherapy.

Keywords

• Cancer immunotherapy
• cytokines
• miRNAs
• natural killer (NK) cells
• tumor microenvironment