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

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.

Therapeutic Implications of Targeting YY1 in Glioblastoma

“…YY1 has been reported to be overexpressed in many cancers, contributing to either tumor suppression or progression depending on the cancer type [ 11 , 12 , 13 ]. As YY1 is overexpressed in GBM, it may play an intrinsic role in the regulation of cell proliferation, viability, migration, metastasis, and resistance to cytotoxic therapies [ 11 , 14 ]. The primary focus of this report is the central role of YY1 expression in GBM in mediating immune evasion and poor prognosis.…”