Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion

Bibliographic Details
Title: Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion
Authors: Yi Liu, Hejing Liu, Miaomiao Ye, Mengying Jiang, Xin Chen, Gendi Song, Huihui Ji, Zhi-wei Wang, Xueqiong Zhu
Source: Cell Death and Disease, Vol 14, Iss 9, Pp 1-14 (2023)
Publisher Information: Nature Publishing Group, 2023.
Publication Year: 2023
Collection: LCC:Cytology
Subject Terms: Cytology, QH573-671
More Details: Abstract Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-β signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-4889
Relation: https://doaj.org/toc/2041-4889
DOI: 10.1038/s41419-023-06149-5
Access URL: https://doaj.org/article/92a2b49f666f4725b305763190ad283c
Accession Number: edsdoj.92a2b49f666f4725b305763190ad283c
Database: Directory of Open Access Journals
More Details
ISSN:20414889
DOI:10.1038/s41419-023-06149-5
Published in:Cell Death and Disease
Language:English