Role of protein arginine methyltransferase 5 in human cancers

Xiao, Wendi; Chen, Xiaoqing; Liu, Lisa; Shu, Yuansen; Zhang, Min; Zhong, Yucheng

doi:10.1016/j.biopha.2019.108790

Cited by 79 publications

(61 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These changes cause suppression of tumor repressor and activation of oncogenes, respectively, finally leading to NSCLC. Accumulating evidence suggests that PRMT5 is an oncoprotein and plays a crucial role in many human cancers through mediating various signaling pathways, which are often involved chromatin remodeling, gene modification and transcription, and protein methylation 15 . To date, it has been clear that dysfunction of PRMT5 has played a part in carcinogenesis and tumor progression, including in gastric cancer, breast cancer, prostate cancer, and lung cancer, especially in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Yang

et al. 2019

Cell Transplant

View full text Add to dashboard Cite

Protein arginine methyltransferase 5 (PRMT5) is implicated in various types of human cancer and tumor development, especially in lung cancer. Nevertheless, it is still unclear whether suppression of PRMT5 could promote lung cancer cell apoptosis and chemosensitivity induced by resveratrol, and the underlying molecular mechanism remains completely unknown. Here, we showed that PRMT5 was overexpressed in human lung cancer tissues and different types of lung cancer cell lines. Moreover, we constructed PRMT5 stable knockdown cell lines (A549 and ASCT-a-1) and investigated the roles of PRMT5 and the related signaling pathway in lung cancer cell apoptosis induced by resveratrol. Our results indicated that inhibition or down-regulation of PRMT5 by GSK591, a PRMT5-specific inhibitor, or shRNAs markedly enhanced cell apoptosis and chemosensitivity stimulated by resveratrol. Further investigation showed that inhibition or down-regulation of PRMT5 further reduced Akt/GSK3β phosphorylation and the downstream targets cyclin D1 and E1 expression upon resveratrol treatment. Our findings suggest that PRMT5 is a pivotal mediator for human lung cancer cell death induced by resveratrol, which also reveals that PRMT5 may serve as a new therapeutic target for the treatment of human lung cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Yang

et al. 2019

Cell Transplant

View full text Add to dashboard Cite

show abstract

“…PRMT5 is an important epigenetic modifying enzyme that catalyses monomethylation and symmetric methylation of arginine residues in both histone and non‐histone proteins 8,9 . Symmetric methylation of specific arginine residues of various proteins by PRMT5 is considered as an essential step in biological processes such as DNA replication and repair, gene transcription, Golgi apparatus and ribosome biogenesis, protein biosynthesis and mRNA splicing 9,10 . Furthermore, extensive studies have demonstrated that PRMT5 is involved in cell‐cycle control, cell migration and cell reprogramming 10 .…”

Section: Introductionmentioning

confidence: 99%

Protein arginine methyltransferase 5 (PRMT5) activates WNT/β‐catenin signalling in breast cancer cells via epigenetic silencing of DKK1 and DKK3

Shailesh

Siveen

Sif

2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

Protein arginine methyltransferase 5 (PRMT5) activity is dysregulated in many aggressive cancers and its enhanced levels are associated with increased tumour growth and survival. However, the role of PRMT5 in breast cancer remains underexplored. In this study, we show that PRMT5 is overexpressed in breast cancer cell lines, and that it promotes WNT/β‐CATENIN proliferative signalling through epigenetic silencing of pathway antagonists, DKK1 and DKK3 , leading to enhanced expression of c‐MYC , CYCLIN D1 and SURVIVIN . Through chromatin immunoprecipitation (ChIP) studies, we found that PRMT5 binds to the promoter region of WNT antagonists, DKK1 and DKK3 , and induces symmetric methylation of H3R8 and H4R3 histones. Our findings also show that PRMT5 inhibition using a specific small molecule inhibitor, compound 5 (CMP5), reduces PRMT5 recruitment as well as methylation of H3R8 and H4R3 histones in the promoter regions of DKK1 and DKK3 , which consequently results in reduced expression CYCLIN D1 and SURVIVIN . Furthermore, CMP5 treatment either alone or in combination with 5‐Azacytidine and Trichostatin A restored expression of DKK1 and DKK3 in TNBCs. PRMT5 inhibition also altered the growth characteristics of breast cancer cells and induced their death. Collectively, these results show that PRMT5 controls breast cancer cell growth through epigenetic silencing of WNT/β‐CATENIN pathway antagonists, DKK1 and DKK3, resulting in up‐regulation of WNT/β‐CATENIN proliferative signalling.

show abstract

“…PRMT5 belongs to the arginine methyltransferase family, which has several functions in oncology, including transcriptional regulation in the nucleus upon arginine methylation of histones and several signal transduction proteins in the cytoplasm 50 . PRMT5 expression did not change in normal CD4 + T cells or samples obtained from patients with ATLL 16 .…”

Section: Roles Of Ndrg2 In Cancermentioning

confidence: 95%

Pathophysiological significance of N‐myc downstream‐regulated gene 2 in cancer development through protein phosphatase 2A phosphorylation regulation

2020

View full text Add to dashboard Cite

show abstract

Role of protein arginine methyltransferase 5 in human cancers

Cited by 79 publications

References 66 publications

PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Protein arginine methyltransferase 5 (PRMT5) activates WNT/β‐catenin signalling in breast cancer cells via epigenetic silencing of DKK1 and DKK3

Pathophysiological significance of N‐myc downstream‐regulated gene 2 in cancer development through protein phosphatase 2A phosphorylation regulation

Contact Info

Product

Resources

About