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Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
Published on: August 7, 2021
Protein arginine methyltransferase (PRMT8) in cancer: Genomic alterations, subcellular dynamics, and clinical
Choo-Yuen Ting1, Sheron Goh Sir Loon2, Lee Bee Sun3
1Department of Pathology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Abstract:
PRMT8 encodes a protein arginine methyltransferase, which is primarily expressed in the brain and nervous system. Several studies have reported its alterations, which have been implicated in various cancers. However, the existing information remains unsystematic and fragmented due to inconsistency in methodology. This review aims to explore PRMT8 gene alterations in humans, their effects on cellular function and physiology, and their clinical implications. We conducted a narrative literature review covering all publications on PRMT8 alterations across different cancer types, their effect on tumour cell characteristics, and their impact on patient prognosis. Reported PRMT8 alterations include mutations, copy number amplifications, and single-nucleotide polymorphisms, which lead to overexpression or downregulation of PRMT8 protein in tumour cells. PRMT8 alterations compromise the efficacy of both chemotherapy and immune checkpoint inhibitor treatment. These alterations enable tumour cells to maintain pluripotency via activation of the PI3K/AKT/SOX2 signalling pathway, thereby promoting cellular proliferation, invasion, and colony formation. Clinically, these PRMT8 alterations drive disease progression and therapy resistance, resulting in poor prognosis and reduced patient survival. These findings underscore the need to incorporate PRMT8 alterations assessment in clinical practice to guide therapeutic decision-making and improve treatment outcomes in affected patient populations.
Insights
Alterations in the PRMT8 gene, a protein arginine methyltransferase, are linked to cancer progression and treatment resistance. Assessing these PRMT8 changes is crucial for improving patient outcomes.
Area of Science:
- Genetics and Molecular Biology
- Cancer Research
- Biochemistry
Background:
- PRMT8 (protein arginine methyltransferase 8) is mainly expressed in the brain and nervous system.
- PRMT8 alterations have been implicated in various cancers, but existing data are fragmented.
- A systematic review is needed to consolidate information on PRMT8 alterations and their clinical significance.
Purpose of the Study:
- To explore human PRMT8 gene alterations.
- To investigate the effects of these alterations on cellular function and physiology.
- To determine the clinical implications of PRMT8 alterations in cancer.
Main Methods:
- Conducted a narrative literature review.
- Included publications on PRMT8 alterations across different cancer types.
- Analyzed the impact on tumor cell characteristics and patient prognosis.
Main Results:
- PRMT8 alterations include mutations, copy number amplifications, and SNPs, leading to altered protein levels.
- These alterations reduce efficacy of chemotherapy and immune checkpoint inhibitors.
- PRMT8 alterations activate the PI3K/AKT/SOX2 pathway, promoting pluripotency, proliferation, invasion, and colony formation.
Conclusions:
- PRMT8 alterations drive cancer progression and therapy resistance, leading to poor prognosis.
- Assessment of PRMT8 alterations is necessary for clinical practice.
- Incorporating PRMT8 assessment can guide treatment decisions and improve patient outcomes.
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