Synaptotagmin 7 in twist-related protein 1-mediated epithelial - Mesenchymal transition of non-small cell lung cancer.

BACKGROUND

Twist-related protein 1 (TWIST1) plays an essential role in the carcinogenesis and metastasis of NSCLC. Our aims were to identify the molecule at the downstream of TWIST1 and to evaluate its potential as a diagnostic and a prognostic marker in NSCLC.

METHODS

The functional genes at the downstream of TWIST1 were obtained via microarray gene expression analyses in the NSCLC cell line. The expression levels of synaptotagmin 7 (SYT7) in a cohort of patients with NSCLC (n = 154) were examined using immunohistochemistry staining and assessed by Kaplan-Meier survival analysis and Cox regression analysis. The effects of SYT7 on the tumorigenesis and metastasis of NSCLC were measured in NSCLC cells. In vivo xenograft lung cancer models were used to study the tumorigenesis role of SYT7.

FINDINGS

We discovered that SYT7 is significantly altered by TWIST1 expression. We further confirmed that SYT7 protein was significantly higher in NSCLC than that in the adjacent normal lung tissue, and higher SYT7 expression was associated with poor survival of NSCLC patients. The protein level of SYT7 was positively correlated with TWIST1 in NSCLC tissue. Functional experiments indicated that SYT7 promoted proliferation, invasion, and metastasis and inhibited cell apoptosis of NSCLC cells in vitro. In vivo experiments showed that shSYT7 inhibited the xenograft tumor growth of NSCLC cells. Knocking down of SYT7 increased the expression of E-cadherin and decreased the level of N-cadherin and Vimentin in cultured cells.

INTERPRETATION

Our data indicate that SYT7 is an important promoter for EMT and tumor progression in NSCLC. FUND: This project was supported by grants from the Major Scientific and Technological Innovation Project of Shandong Province (2018CXGC1212), Science and Technology Foundation of Shandong Province (2014GSF118084, 2016GSF121043), Medical and Health Technology Innovation Plan of Jinan City (201805002) and the National Natural Science Foundation of China (81372333).