The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation
Abstract Background SND1 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 metasta...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01731-3 |
| _version_ | 1797647152282861568 |
|---|---|
| author | Huibian Zhang Min Gao Wenying Zhao Lin Yu |
| author_facet | Huibian Zhang Min Gao Wenying Zhao Lin Yu |
| author_sort | Huibian Zhang |
| collection | DOAJ |
| description | Abstract Background SND1 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. Methods Immunostaining 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. Results The 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. Conclusion SND1 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. |
| first_indexed | 2024-03-11T15:13:11Z |
| format | Article |
| id | doaj.art-e1af911b90244c41a4f682104d352508 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-03-11T15:13:11Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-e1af911b90244c41a4f682104d3525082023-10-29T12:40:53ZengBMCBreast Cancer Research1465-542X2023-10-0125111710.1186/s13058-023-01731-3The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylationHuibian Zhang0Min Gao1Wenying Zhao2Lin Yu3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityAbstract Background SND1 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. Methods Immunostaining 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. Results The 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. Conclusion SND1 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.https://doi.org/10.1186/s13058-023-01731-3SND1Triple-negative breast cancerChromatin architectural interactionMetastasis |
| spellingShingle | Huibian Zhang Min Gao Wenying Zhao Lin Yu The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation Breast Cancer Research SND1 Triple-negative breast cancer Chromatin architectural interaction Metastasis |
| title | The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation |
| title_full | The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation |
| title_fullStr | The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation |
| title_full_unstemmed | The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation |
| title_short | The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation |
| title_sort | chromatin architectural regulator snd1 mediates metastasis in triple negative breast cancer by promoting cdh1 gene methylation |
| topic | SND1 Triple-negative breast cancer Chromatin architectural interaction Metastasis |
| url | https://doi.org/10.1186/s13058-023-01731-3 |
| work_keys_str_mv | AT huibianzhang thechromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT mingao thechromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT wenyingzhao thechromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT linyu thechromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT huibianzhang chromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT mingao chromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT wenyingzhao chromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation AT linyu chromatinarchitecturalregulatorsnd1mediatesmetastasisintriplenegativebreastcancerbypromotingcdh1genemethylation |