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

## TL;DR

This study explores how certain microRNAs and cytokine signaling influence natural killer cell function in cancer, suggesting new ways to boost immunotherapy.

## Contribution

The study identifies specific miRNAs and their regulatory roles in NK cell function through bioinformatic analysis of cytokine-related genes.

## Key findings

- Genes encoding interleukins and IFNG are significantly associated with NK cell infiltration in various cancers.
- Several miRNAs (e.g., hsa-miR-590-3p, hsa-miR-340-5p) potentially regulate NK cell function by targeting these genes.
- mRNA-miRNA co-regulation is highlighted as a key mechanism suppressing NK cells in the tumor microenvironment.

## Abstract

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.

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.

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.

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.