2. Academic Validation
  3. Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion

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

  • Cell Death Dis. 2023 Sep 22;14(9):624. doi: 10.1038/s41419-023-06149-5.
Yi Liu # 1 2,  Hejing Liu # 1,  Miaomiao Ye 1,  Mengying Jiang 1,  Xin Chen 1,  Gendi Song 1,  Huihui Ji 1,  Zhi-Wei Wang 3 4,  Xueqiong Zhu 5
Affiliations

Affiliations

  • 1 Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China.
  • 2 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • 3 Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China. [email protected].
  • 4 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. [email protected].
  • 5 Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China. [email protected].
  • # Contributed equally.
PMID: 37737256 DOI: 10.1038/s41419-023-06149-5
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.

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