Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer

Zheng, Jing1; Huang, Jingyi2; Xia, Jinquan3; Zhou, Wenbin4; Dai, Lingyun3; Lin, Sihang4; Gao, Lin3; Zou, Chang3,5,6

2023-02-06

10.3389/fonc.2023.1038787

Frontiers in Oncology   Impact Factor & Quartile

2234-943X

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.

breast cancer transcription factors biomarker immune checkpoint molecules

SCI

English

First ; Corresponding

Oncology

Oncology

WOS:000937648300001

FRONTIERS MEDIA SA

Web of Science

1.Jinan Univ, Affiliated Hosp Southern Univ Sci & Technol 1, Shenzhen Peoples Hosp, Clin Med Coll 2,Dept Ultrasound, Shenzhen, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Dept Clin Med Res Ctr, Sch Med, Shenzhen, Peoples R China
3.Jinan Univ, Affiliated Hosp Southern Univ Sci & Technol 1, Shenzhen Peoples Hosp, Clin Med Coll 2,Dept Clin Med Res Ctr, Shenzhen, Guangdong, Peoples R China
4.Jinan Univ, Affiliated Hosp Southern Univ Sci & Technol 1, Shenzhen Peoples Hosp, Clin Med Coll 2,Dept Thyroid & Breast Surg,Dept Ge, Shenzhen, Guangdong, Peoples R China
5.Shenzhen Publ Serv Platform Tumor Precis Med & Mol, Shenzhen, Guangdong, Peoples R China
6.Chinese Univ Kong Hong, Sch Life & Hlth Sci, Shenzhen, Guangdong, Peoples R China

Zheng, Jing,Huang, Jingyi,Xia, Jinquan,et al. Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer[J]. Frontiers in Oncology,2023,13.

Zheng, Jing.,Huang, Jingyi.,Xia, Jinquan.,Zhou, Wenbin.,Dai, Lingyun.,...&Zou, Chang.(2023).Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer.Frontiers in Oncology,13.

Zheng, Jing,et al."Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer".Frontiers in Oncology 13(2023).