Protein arginine methyltransferase 5: a potential cancer therapeutic target

Yuan, Yuanyang; Nie, Hong

doi:10.1007/s13402-020-00577-7

Cited by 34 publications

(25 citation statements)

References 88 publications

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“…The driving role of PRMT5 in many types of solid and hematologic cancers has led to efforts to develop PRMT5-selective inhibitors, some of which have now been tested in clinical trials for safety and efficacy (43); however, the effects of PRMT5 on the immune system, especially on CD8 1 T cells, cannot be ignored. Recent studies have reported the suppression of CD8 1 T cells after treatment with PRMT5 inhibitors (EPZ015666 and DST-437) (21,44), and our research provides more information relevant to the application of PRMT5 inhibitors because PRMT5 deletion not only significantly inhibits the survival of CD8 1 T cells but also induces CD8 1 Treg cells, which cause obvious adverse effects.…”

Section: Discussionmentioning

confidence: 99%

PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1+CD8+ Terminal Effector T Cells and Promotes Cancer Development

Zheng

Chen

Zhou

et al. 2022

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1+CD8+ Terminal Effector T Cells and Promotes Cancer Development

Zheng

Chen

Zhou

et al. 2022

The Journal of Immunology

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“…PRMT5 is an emerging epigenetic enzyme that regulates the transcription of target genes through di-methylation of histone residues [ 37 ]. At present, there are highly selective PRMT5 inhibitors developed with PRMT5 as the target, which are used for the treatment of malignant solid tumors and hematological tumors, and have been approved for clinical trials [ 38 ]. This suggests that the use of PRMT5 as a target for the treatment of NPC is of great practical significance.…”

Section: Discussionmentioning

confidence: 99%

Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma

2022

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Targeted therapy is an important therapeutic strategy currently, however, the development of targeted therapy for nasopharyngeal carcinoma (NPC) is relatively lagging. Cullin 4A (CUL4A) was reported to be overexpressed in NPC; nevertheless, the specific role of CUL4A remains unrevealed. NPC cells and tumor-bearing mice were cultivated to explore the role and mechanism of CUL4A in NPC. After evaluating CUL4A levels in NPC cells, functional experiments were carried out to investigate the effects of CUL4A knockdown and overexpression on cell proliferative, invasive and migratory aptitude as well as NF-κB signaling. Following the GeneMANIA database predicted that protein arginine methyltransferase 5 (PRMT5) was downstream of CUL4A, the mediated role of PRMT5 in the regulation of CUL4A on cells was then determined. Moreover, the tumor volumes and weights of tumor-bearing mice were recorded, and the levels of proliferation-, migration-, and NF-κB signaling-related proteins in the tumor were determined. Herein, CUL4A was enhanced in NPC cells, and its knockdown and overexpression separately suppressed and promoted cell proliferative, invasive, and migratory aptitude as well as NF-κB signal activation. Novelty, PRMT5 knockdown reversed the influences of CUL4A overexpression on these aspects. In addition, its knockdown likewise reversed the facilitating impact of CUL4A expression on tumor growth and declined the expression levels of proliferation-, migration-, and NF-κB signaling-related protein in the tumor. Together, this paper indicated that CUL4A promoted the proliferative, invasive, and migratory aptitude of NPC cells as well as tumor growth by promoting PRMT5 to activate NF-κB signaling.

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“…In summary, we identi ed PRMT5 as a critical regulator in decidualization both in mice and humans, partly due to its effect on the NF-κB signaling pathway. Since several PRMT5 inhibitors are in ongoing preclinical and clinical studies for the treatment of cancer 49 , it is worth observing potential side effects on the endometrium and reproductive capacity. In addition, we con rmed that overexpression of PRMT5 rescued the decidualization defect of primary hEnSCs from endometriosis patients, suggesting that promotion of PRMT5 may provide novel therapeutic strategies for the treatment of decidualization defects in infertile women, such as those with endometriosis.…”

Section: Discussionmentioning

confidence: 99%

Endometrial stromal PRMT5 plays a crucial role in decidualization by regulating NF-κB signaling in endometriosis

Yan

Cai

et al. 2022

Preprint

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Decidualization is a prerequisite for successful embryo implantation, in which elongated fibroblast-like endometrial stromal cells differentiate into more rounded decidual cells. Accumulating evidence has stressed the important role of the defective eutopic endometrium in infertility in endometriosis patients. However, the role of arginine methylation in the process of physiological decidualization and pathological decidualization defects is not clear. Here, we observed that the expression level of PRMT5, the main type II PRMT, was decreased in the endometrium of endometriosis patients, predominantly in stromal cells. Compared with the undecidualized state, PRMT5 was increased in the stromal cells of normal secretory endometrium in humans and in the decidua of normal pregnant mice or mice with artificially induced decidualization. The inhibition of PRMT5 resulted in a significant decrease in uterine weight and decidualization-related regulator expression, including FOXO1, HOXA10 and WNT4, in mice and IGFBP1 and prolactin levels in human endometrial stromal cells. Transcriptome analysis showed that decreased PRMT5 activity led to NF-κB signaling activation by inducing p65 translocation to the nucleus, which was also observed in endometriosis patients. Finally, overexpression of PRMT5 rescued the defective expression of IGFBP1 and prolactin in primary endometrial stromal cells from endometriosis patients. Our results indicate that promotion of PRMT5 may provide novel therapeutic strategies for the treatment of decidualization defects in infertile women, such as those with endometriosis.

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Protein arginine methyltransferase 5: a potential cancer therapeutic target

Cited by 34 publications

References 88 publications

PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1+CD8+ Terminal Effector T Cells and Promotes Cancer Development

PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1+CD8+ Terminal Effector T Cells and Promotes Cancer Development

Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma

Endometrial stromal PRMT5 plays a crucial role in decidualization by regulating NF-κB signaling in endometriosis

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