The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation

Breast Cancer Research

Research

Lin Yu¹  Wenying Zhao¹  Min Gao¹  Huibian Zhang¹ 

[1] Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China;Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, 300070, Tianjin, China;Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, 300070, Tianjin, China;

关键词: SND1;    Triple-negative breast cancer;    Chromatin architectural interaction;    Metastasis;   

DOI  :  10.1186/s13058-023-01731-3

 received in 2023-05-21, accepted in 2023-10-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSND1 participates in tumorigenesis, tumour invasion and metastasis in different cancers. Previous studies have shown that SND1 can promote the invasion and migration of breast cancer cells. Triple-negative breast cancer (TNBC) is a specific breast cancer subtype with high metastatic potential and poor prognosis. However, the specific roles and mechanisms of SND1 in TNBC metastasis remain unaddressed.MethodsImmunostaining was used to detect the SND1 expression in tissue samples of 58 TNBC and 10 glioblastomas (GBM) as positive control. The correlation between SND1 expression and patient prognosis was assessed using the Kaplan–Meier estimator. The gene expression was evaluated by qRT-PCR, Western blot and immunofluorescence analyses. Gene Ontology analysis, ChIP, a dual-luciferase reporter assay, EMSA, and 3C analysis were applied to identify SND1-activated target genes. Bisulfite sequencing PCR and MeDIP were used to detect DNA methylation. We also used wound healing, Transwell and orthotopic implantation assays to investigate the function of SND1 in TNBC cell migration and invasion.ResultsThe data of immunohistochemistry manifested that SND1 is the overexpression in metastasized TNBC and an independent factor for TNBC prognosis. SND1 knockdown inhibited the migration and invasion of TNBC cells. We found that SND1 promotes the metastatic phenotype of TNBC cells by epigenetically altering chromatin conformational interactions, which in turn activates DNMT3A transcription. Then, DNMT3A attenuates CCND1 expression by inducing CCND1 gene methylation, leading to TNBC metastasis.ConclusionSND1 can promote the invasion and migration of TNBC cells by promoting DNMT3A expression and suppressing CDH1 activity. SND1 is a potential biomarker and a promising therapeutic target for TNBC.

【 授权许可】

CC BY   
© The Author(s) 2023

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