SYT7 promotes breast cancer cells growth through the PI3K/AKT pathway.

Background: Breast cancer is one of the most malignant tumors in the reproductive system and has a poor prognosis. The aim of this study was to investigate the function and underlying mechanism of synaptotagmin 7 (SYT7) in breast cancer. Methods: We utilized The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter database to assess the correlation between SYT7 expression and the prognosis of breast cancer patients. The efficacy of SYT7 knockdown was evaluated through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Furthermore, we examined the impact of SYT7 on breast cancer cell proliferation and apoptosis using Cell Counting Kit-8 (CCK-8), clone formation assays, and flow cytometry. Through Western blot analysis, we investigated the influence of SYT7 on the expression of apoptosis-related markers and the PI3K/AKT signaling pathway in breast cancer. Results: The TCGA database data analysis revealed a significant up-regulation of SYT7 expression in breast cancer tissues compared to normal tissues (P<0.001). A correlation was observed between SYT7 expression and tumor size (P=0.009), as well as estrogen receptor (ER) expression level (P<0.001) and progesterone receptor (PR) expression level (P<0.001) in breast cancer patients. Analysis of the Kaplan-Meier plotter database indicated that high SYT7 expression was associated with a shorter overall survival (OS) (P=0.009). The mRNA expression results indicated higher SYT7 expression in breast cancer tissues compared to adjacent normal tissues (P=0.005). CCK-8, clone formation assay, and flow cytometry results demonstrated that SYT7 promoted the proliferation and inhibited the apoptosis of breast cancer cells. Western blot assay confirmed the activation of PI3K/AKT signaling by SYT7. Conclusions: The findings suggest that SYT7 is highly expressed in breast cancer and that its high expression is linked to clinical characteristics and prognosis. Inhibition of SYT7 through knockdown can suppress proliferation and promote apoptosis of breast cancer cells, making it a potential target for breast cancer diagnosis and treatment.

The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer.

A disintegrin-like and metalloprotease with therombospondin type1 motif 8 (ADAMTS8) plays an important role in many malignancies. However, the clinical and biological significance of ADAMTS8 in breast cancer remain unknown. In this study, the clinical data from 1066 breast cancer patients were analyzed by The Cancer Genome Atlas (TCGA) database, and were analyzed using the correlation between ADAMTS8 expression and the clinicopathological features and prognoses. The CCK-8 assay, clone formation assay, flow cytometry and Transwell assay were used to characterize the effects of ADAMTS8 on proliferation, migration and invasion of breast cancer cells. Gene set enrichment analysis (GSEA) and western blotting were used to identify the potential molecular mechanism on how ADAMTS8 exert its biological function. ADAMTS8 overexpression correlated longer overall survival (OS) and progression-free survival (PFS). ADAMTS8 was considered as an independent prognostic factor for OS. ADAMTS8 overexpression inhibited breast cancer cell proliferation, migration and invasion in vitro, and induced G2/M cell cycle arrest. ADAMTS8 was also involved in cell cycle regulation and was associated with the EGFR/Akt signaling pathway. ADAMTS8 knockdown showed the reverse effect. Together, the results showed that ADAMTS8 functioned as a tumor suppressor gene (TGS) and could be a prognostic biomarker for breast cancer.

BTNL9 is frequently downregulated and inhibits proliferation and metastasis via the P53/CDC25C and P53/GADD45 pathways in breast cancer.

Breast cancer (BC) threatens the life and health of women worldwide because of its high morbidity and mortality. The present study aimed to explore the biological functions and potential mechanism of BTNL9 in BC. RNA sequence and clinical data extracted from the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) were utilized to analyze the relationship between the expression level of BTNL9 in BC tissues and clinicopathological features and the effects of BTNL9 expression on the prognosis of BC. The diagnostic efficacy of BTNL9 expression was estimated by receiver operating characteristic (ROC) curve analysis. The mRNA and protein expression levels of BTNL9 in BC cell lines and in BC tissue were determined by quantitative real-time PCR (qPCR) and western blotting, respectively. The functions of BTNL9 were measured by colony formation, CCK-8, Transwell, flow cytometry and EdU assays. Western blotting analysis was also performed to explore the latent mechanism of BTNL9. The results showed that the expression of BTNL9 declined in BC tissues and cell lines. Low expression of BTNL9 was significantly associated with early progression of T stage, relapse-free survival (RFS), and poor overall survival (OS). Ectopic expression of BTNL9 inhibited cell proliferation, colony formation and metastasis and induced apoptosis in BC, while knockdown of BTNL9 had the opposite result. Furthermore, BTNL9 blocked BC cells in the G2/M phase via the P53/CDC25C and P53/GADD45 pathways. Our results suggest that BTNL9 may play a tumor-suppressive role in BC and has the potency to become a new biomarker for early BC diagnosis.