PRMT5 (Protein Arginine Methyltransferase 5)

This research demonstrates that [68Ga]Ga-DOTA-FZ-P5R enables rapid imaging of PRMT5-positive tumors. The probe has significant potential to enable individualized and precise diagnosis in patients with PRMT5-positive tumors, define an optimal treatment window, assess therapeutic efficacy, and serve as a predictive imaging modality for tumor resistance.

Inhibiting this signaling axis in combination with radiotherapy impairs intracranial xenograft growth, resulting in significant survival extensions for treated animals. Overall, our findings uncover a previously unrecognized regulatory axis where PRMT5-mediated R124me2s governs YAP activation through a feedback mechanism, presenting novel therapeutic vulnerabilities in GBM.

However, overexpression of FTH1 suppressed ferroptosis and promoted tumor growth. Taken together, PRMT5/RBM15/ferritinophagy signaling can be a potential target for HCC.

These multiomics approaches uncover previously unappreciated roles of PRMT5 as an epigenetic regulator of metabolic homeostasis via coordinating membrane transport, balancing glucose and FA metabolism, and promoting cholesterol biosynthesis. This study highlights a novel mechanism by which protein methylation regulates systemic energy balance.

Moreover, fludarabine targeting STAT1 in combination with anti-PD-1 has a synergetic effect on suppressing tumor growth in mice. Overall, this study reveals that the RNA binding-dependent function of PRMT5 regulates PDCD1 and T cell effector function with WDR77 and identifies potential combinatorial therapeutic strategies for enhancing antitumor efficacy.

In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL.

Notably, genetic or pharmacological inhibition of PRMT5 significantly sensitized NPC cells to paclitaxel, both in vitro and in vivo. Collectively, these results suggest that the PRMT5-KCNMB4 axis plays a crucial role in mediating chemoresistance in NPC and targeting this axis may provide a promising therapeutic strategy for late-stage NPC patients.

Our research provides evidence supporting the synergistic anti-tumor effects of targeting PRMT5 and CDK1 in MTAP-deficient NSCLC.

Our findings demonstrate that decreased PPM1B expression drives the oncogenic activation of the MP/PRMT5 axis. This mechanism contributes to the aggressive nature of SCC, establishing PPM1B as a promising prognostic marker in lung cancer.

miR-770-5p treatment increased the cytoplasmic-to-nuclear ratio of KLF4 and disrupted EGFR localization, demonstrating that miR-770-5p disrupts the PRMT5-KLF4-driven activation of EGFR signaling. These findings indicate that miR-770-5p acts as a tumor suppressor in TNBC by modulating EGFR signaling via PRMT5 and KLF4, emphasizing its potential as a therapeutic target.

Ongoing investigations will be critical to define the therapeutic window of PRMT5 inhibition and to optimize rational combination strategies. This review provides a comprehensive overview of current insights into the oncogenic functions of PRMT5 and highlights emerging therapeutic strategies aimed at improving cancer treatment.

PTBP1 promotes the exclusion of exon 18a which results in the production of the pro-invasive TCF3-18B (E47) isoform which promotes EMT and invasion of breast cancer cells under hypoxia. Collectively, our results indicate PRMT5-mediated symmetric arginine dimethylation of histones regulates alternative splicing of TCF3 gene thereby enhancing EMT and invasion in breast cancer hypoxia.