Comprehensive miRNA profiles revealing cancer-immunity

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Abstract

MicroRNAs (miRNAs) play a pivotal role as post-transcriptional regulators in tumorigenesis, influencing immune pathways in various cancers. However, a systematic identification of potential miRNAs influencing immune pathway activity remains largely elusive. In this study, we presented a comprehensive analysis of miRNAs within 17 immune-related pathways across 32 different cancers. Leveraging GSEA-based and target gene-based computational methods, we identify potential miRNA regulons that are intricately associated with tumor immunity. These miRNAs exhibit a propensity to regulate immune pathways across multiple cancer types. Moreover, miRNA immune regulons manifest expression perturbations in cancer and display significant correlations with immune cell infiltrations. Our study reveals the role of immune-related miRNAs in immune cell development, differentiation, and tumor growth and metastasis dynamics. Furthermore, we optimized two key immunology miRNA regulons, exemplified by hsa-miR-130b-3p and hsa-miR-106b-5p, demonstrating their wide-ranging influence on immune function in tumors. These miRNAs emerged as potential targets for a variety of drugs, offering promise as adjuvant therapy alongside conventional radiotherapy and chemotherapy, as well as contributing to immunotherapeutic approaches. Additionally, our study identifies two molecular subtypes within reproductive system cancers, characterized by distinct tumor mutational burdens (TMB L and TMB H phenotypes). These subtypes exhibit disparities in immune cell infiltrations, checkpoint expression, and prognosis, shedding light on potential avenues for personalized treatment strategies. In summary, our research provides an extensive panorama of miRNA immunology regulons, enhancing our understanding of miRNA function. This knowledge holds significant implications for the development of targeted therapies in tumor immunology and the refinement of personalized treatment approaches.

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