Cross-Talks between RKIP and YY1 through a Multilevel Bioinformatics Pan-Cancer Analysis

SIMPLE SUMMARY: To better understand the potential implications of the cross-talk between RKIP and YY1 in cancer, we comprehensively analyzed different cancer types using bioinformatics approaches. Our study focused on analyzing the expression, mutation, immune infiltration, and drug resistance profiles of the two genes, using large-scale datasets from public repositories such as the Cancer Genome Atlas (TCGA) and the Cancer Proteome Atlas (TCPA). By integrating multiple data sources and applying advanced computational methods, we aimed to identify novel insights into the role of PEBP1/RKIP and YY1 in cancer, as well as potential therapeutic targets and biomarkers. Overall, our study provides new evidence that the cross-talk between RKIP and YY1 might be an important regulator of cancer progression and drug resistance, with potential clinical implications. By elucidating the complex interplay between these two genes, our findings may help in the development of more effective diagnostic and therapeutic strategies for cancer. ABSTRACT: Recent studies suggest that PEBP1 (also known as RKIP) and YY1, despite having distinct molecular functions, may interact and mutually influence each other’s activity. They exhibit reciprocal control over each other’s expression through regulatory loops, prompting the hypothesis that their interplay could be pivotal in cancer advancement and resistance to drugs. To delve into this interplay’s functional characteristics, we conducted a comprehensive analysis using bioinformatics tools across a range of cancers. Our results confirm the association between elevated YY1 mRNA levels and varying survival outcomes in diverse tumors. Furthermore, we observed differing degrees of inhibitory or activating effects of these two genes in apoptosis, cell cycle, DNA damage, and other cancer pathways, along with correlations between their mRNA expression and immune infiltration. Additionally, YY1/PEBP1 expression and methylation displayed connections with genomic alterations across different cancer types. Notably, we uncovered links between the two genes and different indicators of immunosuppression, such as immune checkpoint blockade response and T-cell dysfunction/exclusion levels, across different patient groups. Overall, our findings underscore the significant role of the interplay between YY1 and PEBP1 in cancer progression, influencing genomic changes, tumor immunity, or the tumor microenvironment. Additionally, these two gene products appear to impact the sensitivity of anticancer drugs, opening new avenues for cancer therapy.