Alternatively spliced protein arginine methyltransferase 1 isoform PRMT1v2 promotes the survival and invasiveness of breast cancer cells

Baldwin, R. Mitchell; Morettin, Alan; Paris, Geneviève; Goulet, Isabelle; Côté, Jocelyn

doi:10.4161/cc.22871

Cited by 68 publications

(57 citation statements)

References 78 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RBM15 is involved in chromosome translocation t(1;22), which produces the RBM15-megakaryoblastic leukemia 1 (MKL1) fusion protein associated with acute (A)MKL (19,20). PRMT1 is upregulated in AMKL (21). Consistent with RBM15 knock down in human primary cells, RBM15 knockdown in mice produces a low percentage of mature MKs (22).…”

Section: Discussionmentioning

confidence: 69%

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

Jin

Song

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

Abstract. Protein arginine methyltransferase 1 (PRMT1) serves pivotal roles in various cellular processes. However, its role in megakaryocytic differentiation has not been clearly reported. The aim of the present study was to explore the role of the PRMT-RNA binding motif protein 15 (RBM15) axis in human MK differentiation and the feasibility of targeting PRMT1 for leukemia treatment. In the present study, PRMT1 was overexpressed and the RBM15 protein was knocked down in human umbilical cord blood cluster of differentiation (CD)34 + cells and the cells were then cultured in megakaryocytic differentiation medium. Flow cytometry was used to analyze CD41 and CD42 double-positive cells, as well as the protein expression levels of PRMT1 and RBM15. The results demonstrated that human cord blood CD34 + cells differentiate into mature MKs in high thrombopoitin medium, as demonstrated by CD41 and CD42 expression. Overexpression of PRMT1 in human umbilical cord blood CD34 + cells blocked the maturation of megakaryocytic cells. Knockdown of RBM15 by short hairpin RNA produced less mature MKs. PRMT1 inhibitor rescued PRMT1-blocked megakaryocytic differentiation. These results provide evidence for a novel role of PRMT1 in the negative regulation of megakaryocytic differentiation. PRMT1 may be a therapeutic target for leukemia treatment.

show abstract

Section: Discussionmentioning

confidence: 69%

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

Jin

Song

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…In this study, we focused on an important epigenetic modifier, PRMT7, whose physiologic roles have been established in male imprinted gene methylation, mRNA splicing, DNA repair, and neural cell differentiation (17,(20)(21)(22). To date, PRMT7 has not been studied in association with cancer progression, although other members of the PRMT family, such as PRMT1, PRMT4/CARM1, PRMT5 and PRMT6, have been found to be either upregulated or downregulated in prostate cancer, breast cancer, colon carcinoma, and melanoma (36)(37)(38)(39). Data arising from this study unraveled, for the first time, the functional role of PRMT7 in regulating the EMT in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

PRMT7 Induces Epithelial-to-Mesenchymal Transition and Promotes Metastasis in Breast Cancer

et al. 2014

View full text Add to dashboard Cite

Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E-cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers. Cancer Res; 74(19); 5656-67. Ó2014 AACR.

show abstract

“…[108] PRMT1 has been found to exist as several isoforms, at least two of which are enzymatically inactive. [45a,109] Exact functions of these inactive PRMT1 isoforms remain to be determined. Future research will provide a better understanding of PRMT function in biological and disease processes from a broader and deeper scope.…”

Section: Summary and Perspectivementioning

confidence: 99%

Mechanisms and Inhibitors of Histone Arginine Methylation

Fulton

Brown

Zheng

2018

The Chemical Record

View full text Add to dashboard Cite

Histone methylation plays an important regulatory role in chromatin restructuring and RNA transcription. Arginine methylation that is enzymatically catalyzed by the family of protein arginine methyltransferases (PRMTs) can either activate or repress gene expression depending on cellular contexts. Given the strong correlation of PRMTs with pathophysiology, great interest is seen in understanding molecular mechanisms of PRMTs in diseases and in developing potent PRMT inhibitors. Herein, we reviewed key research advances in the study of biochemical mechanisms of PRMT catalysis and their relevance to cell biology. We highlighted how a random binary, ordered ternary kinetic model for PRMT1 catalysis reconciles the literature reports and endorses a distributive mechanism that the enzyme active site utilizes for multiple turnovers of arginine methylation. We discussed the impacts of histone arginine methylation and its biochemical interplays with other key epigenetic marks. Challenges in developing small-molecule PRMT inhibitors were also discussed.

show abstract

Alternatively spliced protein arginine methyltransferase 1 isoform PRMT1v2 promotes the survival and invasiveness of breast cancer cells

Abstract: Côté (2012) Alternatively spliced protein arginine methyltransferase 1 isoform PRMT1v2 promotes the survival and invasiveness of breast cancer cells, Cell Cycle, 11:24,[4597][4598][4599][4600][4601][4602][4603][4604][4605][4606][4607][4608][4609][4610][4611][4612]

Cited by 68 publications

References 78 publications

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

PRMT7 Induces Epithelial-to-Mesenchymal Transition and Promotes Metastasis in Breast Cancer

Mechanisms and Inhibitors of Histone Arginine Methylation

Contact Info

Product

Resources

About