{"title":"SMYD4通过赖氨酸单甲基化修饰促进MYH9泛素化，抑制乳腺癌进展。","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":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","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":"{\"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\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"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}","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
摘要
背景：乳腺癌是全球女性死亡的主要原因。（SET And MYND Domain Containing 4） SMYD4已被报道为肿瘤抑制因子。然而，SMYD4的分子机制尚不清楚。方法：采用qRT-PCR和western blot检测SMYD4在乳腺癌细胞中的表达水平。体外和体内验证了SMYD4的作用。用共IP法研究SMYD4和MYH9之间的相互作用。通过荧光素酶报告基因实验和ChIP分析检测SMYD4对WNT信号通路的调控作用。结果：本研究发现SMYD4下调与预后不良相关。SMYD4在体内和体外均作为肿瘤抑制因子。SMYD4被发现与下游蛋白MYH9相互作用并阻碍WNT信号通路。进一步的研究表明，SMYD4通过促进MYH9的赖氨酸单甲基化和泛素化降解来阻碍MYH9与CTNNB1启动子区域的结合。结论：这些发现揭示了SMYD4在Wnt/β - catenin信号通路中的新特征，并为基因相互作用提供了新的视角。SMYD4/MYH9/CTNNB1/WNT/β-Catenin信号通路轴的发现提示SMYD4是乳腺癌的潜在治疗靶点。
SMYD4 promotes MYH9 ubiquitination through lysine monomethylation modification to inhibit breast cancer progression.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
