Chang Yuan, Li Yilun, Yang Xiaolu, Zhang Peng, Li Xiaolong, Ma Li
Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.
Department of Breast Surgery, Affiliated Hospital of Hebei Engineering University, Handan, 056000, Hebei, People's Republic of China.
Clin Exp Med. 2025 Jul 14;25(1):248. doi: 10.1007/s10238-025-01792-y.
Breast cancer (BC) is the most common malignant tumor in women worldwide, and exploring new therapeutic targets is a great challenge for BC. SERTA domain containing 4 (SERTAD4) is a member of the SERTAD family, also known as Trip-Br or SEI proteins. The current biological function of SERTAD4 and its role in BC are unclear. The TNMplot, GEPIA2, HPA, TCGA, and Kaplan-Meier Plotter databases and clinical BC samples were used to analyze SERTAD4 expression-clinical correlations in BC. Single-cell sequencing data for BC were obtained from the GEO database to explore the expression, cellular localization, and biological function of SERTAD4 in BC. Additionally, the in vitro effects of siRNA knockdown of SERTAD4 on BC cells were investigated. The TNMplot and GEPIA2 databases indicate that SERTAD4 is upregulated in BC. The HPA database reveals that SERTAD4 protein is primarily localized in the cytoplasm. Analysis of TCGA data demonstrates a negative correlation between SERTAD4 expression and both estrogen receptor (ER) and progesterone receptor (PR) status. These database-derived patterns were consistently observed in our clinical cohort of BC specimens. The Kaplan-Meier Plotter database suggests that high SERTAD4 expression is associated with poor prognosis in BC. Single-cell analysis shows that SERTAD4 is predominantly expressed in epithelial cell subsets, with its expression level correlating with the degree of copy number variation (CNV). Functional enrichment analyses indicate that SERTAD4 can regulate the proliferation and adhesion of epithelial cells and is linked to the PI3K/AKT signaling pathway. In vitro knockdown of SERTAD4 inhibits the migration, invasion, and proliferation of BC cells, accompanied by downregulation of PI3K and AKT protein expression. Molecular docking and Co-immunoprecipitation (Co-IP) analyses revealed an interaction between SERTAD4 and PI3K. The upregulated expression of SERTAD4 in BC is associated with the prognosis of BC and is a potential prognostic factor and therapeutic target for BC.
乳腺癌（BC）是全球女性中最常见的恶性肿瘤，探索新的治疗靶点对乳腺癌来说是一项巨大挑战。含SERTA结构域4（SERTAD4）是SERTAD家族的成员，也被称为Trip-Br或SEI蛋白。目前SERTAD4的生物学功能及其在乳腺癌中的作用尚不清楚。利用TNMplot、GEPIA2、HPA、TCGA和Kaplan-Meier Plotter数据库以及临床乳腺癌样本分析SERTAD4在乳腺癌中的表达与临床的相关性。从GEO数据库获取乳腺癌的单细胞测序数据，以探索SERTAD4在乳腺癌中的表达、细胞定位和生物学功能。此外，还研究了SERTAD4的siRNA敲低对乳腺癌细胞的体外影响。TNMplot和GEPIA2数据库表明SERTAD4在乳腺癌中上调。HPA数据库显示SERTAD4蛋白主要定位于细胞质。对TCGA数据的分析表明SERTAD4表达与雌激素受体（ER）和孕激素受体（PR）状态均呈负相关。这些源自数据库的模式在我们的乳腺癌标本临床队列中得到了一致观察。Kaplan-Meier Plotter数据库表明SERTAD4高表达与乳腺癌预后不良相关。单细胞分析表明SERTAD4主要在上皮细胞亚群中表达，其表达水平与拷贝数变异（CNV）程度相关。功能富集分析表明SERTAD4可调节上皮细胞的增殖和黏附，并与PI3K/AKT信号通路相关。体外敲低SERTAD4可抑制乳腺癌细胞的迁移、侵袭和增殖，同时PI3K和AKT蛋白表达下调。分子对接和免疫共沉淀（Co-IP）分析揭示了SERTAD4与PI3K之间的相互作用。SERTAD4在乳腺癌中的上调表达与乳腺癌预后相关，是乳腺癌潜在的预后因素和治疗靶点。
