SMYD4 promotes MYH9 ubiquitination through lysine monomethylation modification to inhibit breast cancer progression.

IF 7.4 1区医学 Q1 Medicine

Breast Cancer Research Pub Date : 2025-02-10 DOI:10.1186/s13058-025-01973-3

Jin-Shuo Yang, Jun-Ming Cao, Rui Sun, Xue-Jie Zhou, Zhao-Hui Chen, Bo-Wen Liu, Xiao-Feng Liu, Yue Yu, Xin Wang

{"title":"SMYD4 promotes MYH9 ubiquitination through lysine monomethylation modification to inhibit breast cancer progression.","authors":"Jin-Shuo Yang, Jun-Ming Cao, Rui Sun, Xue-Jie Zhou, Zhao-Hui Chen, Bo-Wen Liu, Xiao-Feng Liu, Yue Yu, Xin Wang","doi":"10.1186/s13058-025-01973-3","DOIUrl":null,"url":null,"abstract":"Background: Breast cancer is the leading cause of female mortality worldwide. (SET And MYND Domain Containing 4) SMYD4 has been reported to be a tumour suppressor. However, the molecular mechanism of SMYD4 remains unclear.Methods: The expression level of SMYD4 in breast cancer cells was detected by qRT-PCR and western blot. The effect of SMYD4 was verified in vitro and in vivo. The interaction between SMYD4 and MYH9 was investigated by co‑IP assay. The regulation of SMYD4 on WNT signaling pathway was detected by luciferase reporter assay and ChIP analysis.Results: This study found that SMYD4 downregulation was associated with poor prognosis. SMYD4 was performed as a tumor suppressor both in vitro and in vivo. SMYD4 was found to interact with the downstream protein MYH9 and impede WNT signaling pathway. Further studies revealed that SMYD4 impeded the binding of MYH9 to the CTNNB1 promoter region by promoting lysine monomethylation and ubiquitination degradation of MYH9.Conclusions: These findings reveal the emerging character of SMYD4 in Wnt/β‑catenin signaling and bring new sights of gene interaction. The discovery of this SMYD4/MYH9/CTNNB1/WNT/β-Catenin signalling pathway axis suggests that SMYD4 is a potential therapeutic target for breast cancer.","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"20"},"PeriodicalIF":7.4000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812198/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13058-025-01973-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Breast cancer is the leading cause of female mortality worldwide. (SET And MYND Domain Containing 4) SMYD4 has been reported to be a tumour suppressor. However, the molecular mechanism of SMYD4 remains unclear.

Methods: The expression level of SMYD4 in breast cancer cells was detected by qRT-PCR and western blot. The effect of SMYD4 was verified in vitro and in vivo. The interaction between SMYD4 and MYH9 was investigated by co‑IP assay. The regulation of SMYD4 on WNT signaling pathway was detected by luciferase reporter assay and ChIP analysis.

Results: This study found that SMYD4 downregulation was associated with poor prognosis. SMYD4 was performed as a tumor suppressor both in vitro and in vivo. SMYD4 was found to interact with the downstream protein MYH9 and impede WNT signaling pathway. Further studies revealed that SMYD4 impeded the binding of MYH9 to the CTNNB1 promoter region by promoting lysine monomethylation and ubiquitination degradation of MYH9.

Conclusions: These findings reveal the emerging character of SMYD4 in Wnt/β‑catenin signaling and bring new sights of gene interaction. The discovery of this SMYD4/MYH9/CTNNB1/WNT/β-Catenin signalling pathway axis suggests that SMYD4 is a potential therapeutic target for breast cancer.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Breast Cancer Research ONCOLOGY-

CiteScore

12.00

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.