Author ORCID Identifier

https://orcid.org/0009-0007-5801-6290

Date Available

12-10-2025

Year of Publication

2025

Document Type

Master's Thesis

Degree Name

Master of Science in Medical Sciences (MSMS)

College

Medicine

Department/School/Program

Medical Sciences

Faculty

Tadahide Izumi

Faculty

Subbarao Bondada

Faculty

Jessica Blackburn

Abstract

Protein Arginine Methyltransferase 5 (PRMT5) is a member of PRMT family that controls both intrinsic and extrinsic oncogenic processes [1]. Protein arginine methyltransferase 5 (PRMT5) is a type II methyltransferase that exerts widespread influence over gene expression, splicing, DNA repair, and immune regulation through symmetric dimethylation of arginine residues on histone and non-histone proteins [2]. The addition of methyl groups induces gene silencing through producing dictatorial histone marks like H2AR3ne2s, H3R8me2s and H4R3mes [3], which act as epigenetic repressive marks on gene promoters. In non-histone proteins, PRMT5 can methylate and regulate transcription factor proteins such as p53, E2F1, and p65, which play critical roles in cell life and death decisions [3].

PRMT5 is a key epigenetic regulator that broadly influences cellular processes, including transcription and metabolism, thereby promoting cancer development and therapy resistance [2], [4]. Recent studies have uncovered its emerging role as a central node linking innate immune activation, immune evasion, and immune suppression in cancer. In the context of inflammation, emerging studies identify PRMT5 as key modulator of immune cell function through epigenetic regulation. Antigen Presenting Cells (APCs) rely on coordinated expression of MHC and co-stimulatory molecules for effective antigen presentation and T cell activation [5], [6], [7], [8]. Given PRMT5’s established role in gene repression via symmetric dimethylation of histone arginine residues, we hypothesize that PRMT5 limits the transcription of immune-stimulatory genes during APC development and activation. This suppression may represent a mechanism by which tumors exploit PRMT5 to dampen immune surveillance leading to immune evasion.

This review provides a comprehensive analysis that integrates current findings to highlight the emerging role of PRMT5 as an epigenetic regulator that modulates inflammatory signaling and enables immune evasion in cancer. Special emphasis is placed on the intracellular signaling pathways such as the mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB), and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways and immune checkpoint molecules that either by amplifying or repressing their downstream effects. Based on our unpublished experimental data, we further postulate that PRMT5 influences expression of co-stimulatory molecules such as CD40 and CD80, cytokine production, immune cell activation, and the balance between immune surveillance and immune suppression. These mechanistic insights support the hypothesis that targeting PRMT5 could restore effective antigen presentation and enhance anti-tumor immunity.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2025.524

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