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. 2021 Dec 20;21(1):696.
doi: 10.1186/s12935-021-02394-w.

SYT7 acts as an oncogene and a potential therapeutic target and was regulated by ΔNp63α in HNSCC

You Fu #  1   2 , Guocai Tian #  1   2 , Zhiyuan Zhang  3   4 , Xiao Yang  5   6
Affiliations

SYT7 acts as an oncogene and a potential therapeutic target and was regulated by ΔNp63α in HNSCC

You Fu et al. Cancer Cell Int. .

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) are one of the most common types of head and neck cancer, and it is urgent to find effective treatment for advanced patients. Exploring developing and progressing mechanisms of HNSCC could provide a theoretical basis to find new therapeutic targets.

Methods: In our research, we performed a whole-gene expression profile microarray analysis to identify differential expression genes between squamous cell carcinoma cells and ΔNp63 alpha (ΔNp63α) knockdown cells. As a result, an important gene Synaptotagmin VII (SYT7) was screened out.

Results: SYT7 knockdown affected the proliferation, apoptosis and cell cycle of squamous cell carcinoma cells. The rescue experiment in vitro with ΔNp63α and SYT7 double knockdown resulted in partial reversion of ΔNp63α-induced phenotypes. This was also confirmed by experiments in vivo.

Conclusions: Taken together, we found that ΔNp63α could inhibit the occurrence and progression of HNSCC throughout downregulating the expression of SYT7. Therefore, SYT7/ΔNp63α axis could be a potential therapeutic target for clinical treatment of HNSCC.

Keywords: Head and neck squamous cell carcinoma; SYT7; TCGA, microarray; ΔNp63 alpha.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overexpression of ΔNP63α inhibited growth and migration of HN6 and CAL-27 cells. A Detection of cell proliferation of HN6 cells by Celigo cell count. B Detection of cell proliferation of CAL-27 cells by Celigo cell count. C Wound-healing assay of HN6 cells. D Wound-healing assay of CAL-27 cells (n = 3). Bars show the mean ± SD. ***Represents p < 0.001. Scale bar = 100 μm
Fig. 2
Fig. 2
Overexpression of ΔNP63α induced cell apoptosis and reduced the proportion of tumor cells in G1 phase in HN6 and CAL-27 cells. A Apoptosis assay of HN6 cells. B Apoptosis assay of CAL-27 cells. C Cell cycle detection of HN6 cells. D Cell cycle detection of CAL-27 cells (n = 3). Bars show the mean ± SD. **Represents p < 0.01, ***represents p < 0.001
Fig. 3
Fig. 3
Bioinformatic analysis of ΔNP63α-knockdown cells. A IPA analysis of ΔNP63α-knockdown cells. B Protein expression of between shCtrl cells and ΔNP63α-knockdown cells. C mRNA expression of between shCtrl cells and ΔNP63α-knockdown cells. D Microarray detection of SYT7 expression in HNSCC samples and paired normal tissues. E GO enrichment of differential genes. F KEGG pathway enrichment of differential genes
Fig. 4
Fig. 4
Knockdown of SYT7 suppressed the proliferation of HN6 and CAL-27 cells and ΔNP63α-SYT7 double knockdown could partially rescue this phenotype. A, B Detection of cell proliferation of SYT7-knockdown HN6 cells by Celigo cell count. C, D Detection of cell proliferation of ΔNP63α SYT7 double knockdown HN6 cells by Celigo cell count. E, F Detection of cell proliferation of SYT7-knockdown CAL-27 cells by Celigo cell count. G, H Detection of cell proliferation of ΔNP63α SYT7 double knockdown CAL-27 cells by Celigo cell count (n = 3). Bars show the mean ± SD. ***Represents p < 0.001. Scale bar = 100 μm
Fig. 5
Fig. 5
Knockdown of SYT7 induced cell apoptosis and influenced cell cycle of HN6 and CAL-27 cells and ΔNP63α-SYT7 double knockdown could partially rescue this phenotype. A Wound-healing analysis of SYT7-knockdown HN6 cells. B Wound-healing analysis of ΔNP63α SYT7 double knockdown HN6 cells. C Wound-healing analysis of SYT7-knockdown CAL-27 cells. D Wound-healing analysis of ΔNP63α SYT7 double knockdown CAL-27 cells. E Apoptosis assay of SYT7-knockdown and shCtrl HN6 cells. F Apoptosis assay of ΔNP63α SYT7 double knockdown and shCtrl HN6 cells. G Apoptosis assay of SYT7-knockdown and shCtrl CAL-27 cells. H Apoptosis assay of ΔNP63α SYT7 double knockdown and shCtrl CAL-27 cells. I Cell cycle detection of SYT7-knockdown and shCtrl HN6 cells. J Cell cycle detection of ΔNP63α SYT7 double knockdown and shCtrl HN6 cells. K Cell cycle detection of SYT7-knockdown and shCtrl CAL-27 cells. L Cell cycle detection of ΔNP63α SYT7 double knockdown and shCtrl CAL-27 cells (n = 3). Bars show the mean ± SD. *Represents p < 0.05, **represents p < 0.01, ***represents p < 0.001, ****represents p < 0.0001. Scale bar = 100 μm
Fig. 6
Fig. 6
Establishment of SYT7-knockdown xenograft tumor model in nude mice. A–C In vivo imaging analysis of nude mice after SYT7 knockdown. D Tumor samples from nude mice. E Tumor growth curve in nude mice with SYT7 knockdown. F Weight of tumors collected from nude mice (n = 10). Bars show the mean ± SD. **Represents p < 0.01, ***represents p < 0.001
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