Comprehensive Analysis of Correlations in the Expression of miRNA Genes and Immune Checkpoint Genes in Bladder Cancer Cells

Abstract

Personalised medicine is the future and hope for many patients, including those with cancers. Early detection, as well as rapid, well-selected treatment, are key factors leading to a good prognosis. MicroRNA mediated gene regulation is a promising area of development for new diagnostic and therapeutic methods, crucial for better prospects for patients. Bladder cancer is a frequent neoplasm, with high lethality and lacking modern, advanced therapeutic modalities, such as immunotherapy. MicroRNAs are involved in bladder cancer pathogenesis, proliferation, control and response to treatment, which we summarise in this perspective in response to lack of recent review publications in this field. We further performed a correlation-based analysis of microRNA and gene expression data in bladder cancer (BLCA) TCGA dataset. We identified 27 microRNAs hits with opposite expression profiles to genes involved in immune response in bladder cancer, and 24 microRNAs hits with similar expression profiles. We discuss previous studies linking the functions of these microRNAs to bladder cancer and assess if they are good candidates for personalised medicine therapeutics and diagnostics. The discussed functions include regulation of gene expression, interplay with transcription factors, response to treatment, apoptosis, cell proliferation and angiogenesis, initiation and development of cancer, genome instability and tumour-associated inflammatory reaction.

Immune Checkpoint and Other Receptor-Ligand Pairs Modulating Macrophages in Cancer: Present and Prospects

“…However, some problems remain unsolved: (1) Very little is known about the downstream crossover signal transmission pathway of IC on TAMs or tumor cells, although there has been a lot of bioinformatic analysis of IC expression profiles [ 218 , 219 ]. (2) Lack of insight into the regulatory network between TAMs and other immune cells under immunosuppressive conditions.…”

Transcriptional and post-transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse

“…Recently, we performed a comprehensive bioinformatical analysis of the correlation between the expression of 21 genes known to be involved in the immunological synapse and miRNAs in bladder cancer (Dobosz et al 2020 ; Stempor et al 2021 ). This analysis revealed that the expression of 19 miRNAs positively correlated with checkpoint gene expression, and 27 other miRNAs negatively, indicating a high interdependency of these components in a well-connected correlation network (Stempor et al 2021 ).…”

“…Recently, we performed a comprehensive bioinformatical analysis of the correlation between the expression of 21 genes known to be involved in the immunological synapse and miRNAs in bladder cancer (Dobosz et al 2020 ; Stempor et al 2021 ). This analysis revealed that the expression of 19 miRNAs positively correlated with checkpoint gene expression, and 27 other miRNAs negatively, indicating a high interdependency of these components in a well-connected correlation network (Stempor et al 2021 ). Building on the prior indication that miRNA profiles might be more useful for cancer diagnosis and prognosis than those based on mRNA (Esquela-Kerscher and Slack 2006 ), combinational miRNA-mRNA profiles might therefore provide an added value for cancer diagnosis and selection of optimal strategy for immunotherapy.…”