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. 2024 Jun 30;13(6):2767-2778.
doi: 10.21037/tcr-24-7. Epub 2024 Jun 6.

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

Chenghao Luo  1   2 , Qingfan Mo  1   2 , Guosheng Ren  1   2
Affiliations

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

Chenghao Luo et al. Transl Cancer Res. .

Abstract

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.

Keywords: PI3K/AKT signal; Synaptotagmin 7 (SYT7); apoptosis; breast cancer; proliferation.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-7/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
SYT7 is overexpressed in human breast cancer tissues and associated with clinical outcomes. (A) Analysis of SYT7 expression in 108 pairs of matched breast cancer tissues and adjacent tissues using the TCGA database. (B) Analysis of SYT7 expression in 1,096 breast cancer tissues and 112 normal tissues using the TCGA database. (C) Utilizing the Kaplan-Meier plotter database to examine the association between SYT7 expression and OS or RFS. SYT7, synaptotagmin 7; OS, overall survival; RFS, recurrence-free survival; HR, hazard ratio; CI, confidence interval; TCGA, The Cancer Genome Atlas.
Figure 2
Figure 2
SYT7 is highly expressed in both breast cancer cells and tissues. (A) In our study, qPCR was employed to identify the presence of mRNA of SYT7 in different cell lines of human breast cancer. (B) Additionally, we conducted qPCR analysis to assess the mRNA expression of SYT7 in 22 pairs of human breast cancer tissues and their respective nearby tissues. *, P<0.05 (P=0.02); and ***, P<0.001. SYT7, synaptotagmin 7; qPCR, quantitative polymerase chain reaction.
Figure 3
Figure 3
Knockdown efficiency of three SYT7 siRNAs in different breast cancer cells by qPCR and western blot. For all panels, ***, P<0.001. SYT7, synaptotagmin 7; NC, negative control; siRNA, small interfering RNA; qPCR, quantitative polymerase chain reaction.
Figure 4
Figure 4
Knockdown of SYT7 inhibited the proliferation and colony formation of MCF-7 and T47D cells. (A) The CCK-8 assay was implemented to evaluate the activity of MCF-7 and T47D cells. (B) In order to assess the cell colony formation, a colony formation experiment was carried out in MCF-7 and T47D cells that were transfected with si-SYT7 (cells were stained with crystal violet staining solution). (C) To quantify the distribution, flow cytometry analysis was conducted. For all panels, *, P<0.05 (P=0.03); **, P<0.01; and ***, P<0.001 (P=0.008). OD, optical density; NC, negative control; SYT7, synaptotagmin 7; CCK-8, Cell Counting Kit-8.
Figure 5
Figure 5
Knockdown of SYT7 promotes the apoptosis of MCF-7 and T47D cells. (A) The percentage of cells undergoing apoptosis was analyzed using flow cytometry in MCF-7 and T47D cells transfected with si-SYT7. (B) Additionally, western blot was employed to detect the expression of proteins associated with apoptosis. ***, P<0.001. NC, negative control; SYT7, synaptotagmin 7; FITC, fluorescein isothiocyanate.
Figure 6
Figure 6
The expression of PI3K, p-PI3K, AKT and p-AKT were detected by western blot in MCF-7 and T47D cells. NC, negative control.
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