Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer
IntroductionTumorigenesis in breast cancers usually accompanied by the dysregulation of transcription factors (TFs). Abnormal amplification of TFs leads aberrant expression of its downstream target genes. However, breast cancers are heterogeneous disease with different subtypes that have distinguish...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1038787/full |
| _version_ | 1811170982114623488 |
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| author | Jing Zheng Jingyi Huang Jinquan Xia Wenbin Zhou Lingyun Dai Sihang Lin Lin Gao Chang Zou Chang Zou Chang Zou |
| author_facet | Jing Zheng Jingyi Huang Jinquan Xia Wenbin Zhou Lingyun Dai Sihang Lin Lin Gao Chang Zou Chang Zou Chang Zou |
| author_sort | Jing Zheng |
| collection | DOAJ |
| description | IntroductionTumorigenesis in breast cancers usually accompanied by the dysregulation of transcription factors (TFs). Abnormal amplification of TFs leads aberrant expression of its downstream target genes. However, breast cancers are heterogeneous disease with different subtypes that have distinguished clinical behaviours, and the identification of prognostic TFs may enable to provide diagnosis and treatment of breast cancer based on subtypes, especially in Basal-like breast cancer.MethodsThe RNA-sequencing was performed to screen differential TFs in breast cancer subtypes. The GEPIA dataset analysis was used to analyze the genes expression in invasive breast carcinoma. The expression of MYBL2, HOXC13, and E2F8 was verified by qRT-PCR assay in breast cancers. The depiction analysis of co-expressed proteins was revealed using the STRING datasets. The cellular infiltration level analysis by the TISIDB and TIMER databases. The transwell assay was performed to analyze cellular migration and invasion. CCK-8 assay was used to evaluate cellular drug susceptibility for docetaxel treatment. Predicted targeted drugs in breast cancers by GSCA Lite database online.ResultsKaplan-Meier plotter suggested that high expression of both E2F8 and MYBL2 in Basal-like subtype had a poor relapse-free survival. Functional enrichment results identified that apoptosis, cell cycle, and hormone ER pathway were represented the crucial regulation pathways by both E2F8 and MYBL2. In the meantime, database analysis indicated that high expression of E2F8 responded to chemotherapy, while those patients of high expression of MYBL2 responded to endocrinotherapy, and a positive correlation between the expression of E2F8 and PD-L1/CTLA4. Our cell line experiments confirmed the importance of E2F8 and MYBL2 in proliferation and chemotherapy sensitivity, possibly, the relationship with PD-L1. Additionally, we also observed that the up-regulation of E2F8 was accompanied with higher enrichments of CD4+ T cells and CD8+ T cells in breast cancers. ConclusionTaken together, our findings elucidated a prospective target in Basal-like breast cancer, providing underlying molecular biomarkers for the development of breast cancer treatment. |
| first_indexed | 2024-04-10T17:05:51Z |
| format | Article |
| id | doaj.art-14db2005a4e74c64a03b7a156c00ee0f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T17:05:51Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-14db2005a4e74c64a03b7a156c00ee0f2023-02-06T04:42:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.10387871038787Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancerJing Zheng0Jingyi Huang1Jinquan Xia2Wenbin Zhou3Lingyun Dai4Sihang Lin5Lin Gao6Chang Zou7Chang Zou8Chang Zou9Department of Ultrasound, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaDepartment of Clinical Medical Research Center, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaDepartment of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaDepartment of Thyroid and Breast Surgery, Department of General Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaDepartment of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaDepartment of Thyroid and Breast Surgery, Department of General Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaDepartment of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaDepartment of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, ChinaShenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen, Guangdong, ChinaSchool of Life and Health Sciences, The Chinese University of Kong Hong, Shenzhen, Guangdong, ChinaIntroductionTumorigenesis in breast cancers usually accompanied by the dysregulation of transcription factors (TFs). Abnormal amplification of TFs leads aberrant expression of its downstream target genes. However, breast cancers are heterogeneous disease with different subtypes that have distinguished clinical behaviours, and the identification of prognostic TFs may enable to provide diagnosis and treatment of breast cancer based on subtypes, especially in Basal-like breast cancer.MethodsThe RNA-sequencing was performed to screen differential TFs in breast cancer subtypes. The GEPIA dataset analysis was used to analyze the genes expression in invasive breast carcinoma. The expression of MYBL2, HOXC13, and E2F8 was verified by qRT-PCR assay in breast cancers. The depiction analysis of co-expressed proteins was revealed using the STRING datasets. The cellular infiltration level analysis by the TISIDB and TIMER databases. The transwell assay was performed to analyze cellular migration and invasion. CCK-8 assay was used to evaluate cellular drug susceptibility for docetaxel treatment. Predicted targeted drugs in breast cancers by GSCA Lite database online.ResultsKaplan-Meier plotter suggested that high expression of both E2F8 and MYBL2 in Basal-like subtype had a poor relapse-free survival. Functional enrichment results identified that apoptosis, cell cycle, and hormone ER pathway were represented the crucial regulation pathways by both E2F8 and MYBL2. In the meantime, database analysis indicated that high expression of E2F8 responded to chemotherapy, while those patients of high expression of MYBL2 responded to endocrinotherapy, and a positive correlation between the expression of E2F8 and PD-L1/CTLA4. Our cell line experiments confirmed the importance of E2F8 and MYBL2 in proliferation and chemotherapy sensitivity, possibly, the relationship with PD-L1. Additionally, we also observed that the up-regulation of E2F8 was accompanied with higher enrichments of CD4+ T cells and CD8+ T cells in breast cancers. ConclusionTaken together, our findings elucidated a prospective target in Basal-like breast cancer, providing underlying molecular biomarkers for the development of breast cancer treatment.https://www.frontiersin.org/articles/10.3389/fonc.2023.1038787/fullbreast cancertranscription factorsE2F8biomarkerimmune checkpoint molecules |
| spellingShingle | Jing Zheng Jingyi Huang Jinquan Xia Wenbin Zhou Lingyun Dai Sihang Lin Lin Gao Chang Zou Chang Zou Chang Zou Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer Frontiers in Oncology breast cancer transcription factors E2F8 biomarker immune checkpoint molecules |
| title | Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer |
| title_full | Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer |
| title_fullStr | Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer |
| title_full_unstemmed | Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer |
| title_short | Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer |
| title_sort | transcription factor e2f8 is a therapeutic target in the basal like subtype of breast cancer |
| topic | breast cancer transcription factors E2F8 biomarker immune checkpoint molecules |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1038787/full |
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