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. 2024 Jan 19;10(3):e24806.
doi: 10.1016/j.heliyon.2024.e24806. eCollection 2024 Feb 15.

SYT7 (synaptotagmin 7) promotes cervical squamous cell carcinoma

Jinbing Huang  1 , Wensheng Xu  1 , Qiaoqiao Huang  1 , Erling Chen  1 , Junying Chen  1
Affiliations

SYT7 (synaptotagmin 7) promotes cervical squamous cell carcinoma

Jinbing Huang et al. Heliyon. .

Abstract

Cervical squamous cell carcinoma (CESC) ranks among the primary contributors to global cancer-associated mortality. However, the role mediated by synaptotagmin 7 (SYT7) in CESC remains unclear. Our study employed immunohistochemistry to assess the level of SYT7 expression in the tissue microarray. Furthermore, lentiviral shRNA transduction was utilized to establish SYT7 knockdown cell line models based on HeLa and SiHa cell lines. The functional impacts of silencing SYT7 expression in vitro were evaluated. A subcutaneous xenograft model was employed to examine the tumorigenic potential of cells with or without SYT7. The content of SYT7 in CESC tissues was significantly elevated compared to adjacent normal tissues. Functionally, silencing SYT7 in HeLa and SiHa cells suppressed cell proliferation, colony formation ability, and apoptosis enhancement. Additionally, cells with suppressed SYT7 also exhibited inhibited cell migration and invasion. In vivo experiments demonstrated the loss of tumorigenic ability in SYT7 knockdown cells and suppressed tumor growth. Quantitative PCR PrimeView PathArray and apoptosis antibody array analyses revealed that upon elimination of SYT7, there was a significant upregulation observed in Caspase 8, TNF-R1 (TNF receptor superfamily member 1A), and HSPA5 (heat shock protein family A [Hsp70] member 5), while TGFBI (transforming growth factor beta-induced), RPL31 (ribosomal protein L31), LUM (lumican), HSDL2 (hydroxysteroid dehydrogenase-like 2), ITGB5 (integrin subunit beta 5), and Smad2 (SMAD family member2) were downregulated. Overall, we have demonstrated the tumor-promoting functions of SYT7 in CESC.

Keywords: Apoptosis; Cervical squamous cell carcinoma; Migration; Proliferation; SYT7.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Junying Chen reports financial support was provided by National Natural Science Foundation of China. Junying Chen reports financial support was provided by China Postdoctoral Science Foundation General Project. Junying Chen reports financial support was provided by Guangxi Medical University Training Program for Distinguished Young Scholars. Junying Chen reports financial support was provided by medical and health appropriate technology development and promotion application project of Guangxi Province. Junying Chen reports financial support was provided by Guangxi Science and Technology Project.

Figures

Fig. 1
Fig. 1
Overexpression of SYT7 in CESC tissues compared to the adjoining normal tissues. SYT7 protein expression in CESC tissues and adjoining normal tissues were determined via IHC with three representative cases in each category for presentation (200 × , left, 400 × , right).
Fig. 2
Fig. 2
SYT7 silencing suppressed cell growth and promoted cell apoptosis. A. The SYT7 knockdown inhibited cell proliferation during MTT assay (HeLa: P < 0.001; SiHa: P < 0.001); B. The SYT7 knockdown suppressed colony formation ability (HeLa: P < 0.001; SiHa: P < 0.001); C. The SYT7 silencing induced apoptosis in HeLa (P < 0.001) and SiHa (P < 0.001) cell lines. (*P < 0.05; **P < 0.01, ***P < 0.001, ****P < 0.0001).
Fig. 3
Fig. 3
SYT7 knockdown inhibited cell migration and cell invasion. A. SYT7 silencing inhibited cell migration as determined by wound healing assay in HeLa (P < 0.001) and SiHa (P < 0.001) cells; B. The SYT7 knockdown in HeLa and SiHa cells inhibited cell invasion (both P < 0.001). (*P < 0.05; **P < 0.01, ***P < 0.001, ****P < 0.0001).
Fig. 4
Fig. 4
SYT7 silencing inhibited tumorigenesis in a subcutaneous xenograft mouse model. A. Representative bioluminescence imaging of a subcutaneous xenograft mouse model and solid tumor at harvest; B Representative tumor growth of subcutaneous xenograft mouse model. C. Growth curve of tumor volume measured periodically (V = ½ (Length × Width2)); D. Total bioluminescent intensity measured at harvest (P < 0. 0.05). E. Tumor weight (g) measured at harvest (P < 0.001); F. H&E and Ki67 staining of tumor sections derived from xenograft mouse models; (*P < 0.05; **P < 0.01, ***P < 0.001, ****P < 0.0001).
Fig. 5
Fig. 5
Screening of downstream targets of SYT7 by the GeneChip PrimeView PathArray™. A. The interaction network between the target gene SYT7 and differentially expressed genes. B. Quantitative PCR validation of PathArray identified the differentially expressed genes, which were downstream of SYT7; C. Western blot validation of downstream targets.
Fig. 6
Fig. 6
Identification of downstream targets of SYT7 by Human Apoptosis Antibody Array. A. Comparison between the shCtrl and shSYT7 proteins (SiHa) using Human Apoptosis Antibody array with densitometry quantification is shown in the right panel (Top 10 candidates listed); B. Grey value of top 10 candidates identified in the Human Apoptosis Antibody Array; C. Western blot validation of potential downstream targets. D. The quantification of the bands of CALM1, HSPA5, IL1RAP, ITGB5 and smad2 (*P < 0.05; **P < 0.01, ***P < 0.001, ****P < 0.0001).
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