Multiomics analysis identifies EBF1 and MYB as key regulators of PD-1 gene in breast cancer

Abstract

Author(s): Priyanka Mishra, Koteswari Peddi, Prathyash Ushus MJ, Akhileshwar Namani, Sivakumar Kandula, Satyanarayana Swamy Cheekatla

Programmed cell death protein 1 (PD-1), an immune suppressant controls the effector activity of T lymphocytes through interaction with Programmed death-ligand 1 protein (PD-L1). The T cells become fatigued as a result of this engagement. However, it is still unknown what molecular processes cause T cells to attain a state of exhaustion. Even the PD-1 Transcription Factor’s (TFs) molecular roles are unclear. Consequently, to understand the underlying processes of PD-1 expression in T cells, we sought to identify novel PD-1 Transcription Factors (TFs). Using computational techniques, we collected the data of PD-1 TFs and assessed their biological activities, related pathways, and interaction matrix. Two TFs, EBF1 and MYB, that were experimentally found to interact with PD-1 were found in several open databases. The sequence of PD-1, predicted transcription factors of PD-1, and binding strength and affinities of the TFs to PD-1 were all determined using the online tools ENSEMBL, TRAP, and CISTROME. Understanding the binding pattern of PD-1 and its TFs in breast cancer is made easier by the information provided. Associated pathways were discovered using integrated network analysis of PD-1 and its co-expressed genes. Additionally, expression analysis of PD-1 and TFs was conducted using the cBioportal and TIMER 2.0 web tool to investigate any potential correlations. This further demonstrated the strong relationship between EBF1 and MYB, which influences how PD-1 is expressed. The study argues for better comprehension and interpretation of the biological functions and pathways of PD-1, EBF1, and MYB, which would make them more useful as breast cancer biomarkers and therapeutic targets.

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