Silencing of STX4 inhibits the proliferation, migration and invasion of ovarian cancer cells via EMT/MMP2/ CCND1 signaling pathway.

BACKGROUND

Ovarian cancer (OC) is one of the most common malignant tumors of the female reproductive system and 55-75% of patients relapse after surgery and standard postoperative chemotherapy and radiotherapy. Syntaxin4 (STX4) is localized in the plasma membrane and plays a role in the occurrence, development, invasion and metastasis of cancer cells.

OBJECTIVE

To investigate the changes in the biological behavior and effects of STX4 gene silencing on the invasion and metastasis of OC cell lines.

METHODS

The proliferation, migration and invasion abilities of two groups of OC cell lines SK-OV-3 and CAOV-3 constructed with an interfering plasmid (pLVX-shRNA1-STX4-shRNA) and a negative control plasmid (pLVX-shRNA1-nonspecific-shRNA), were examined via Cell Counting Kit-8, Transwell and scratch assays. The EMT markers vimentin and E-cadherin, MMPs (MMP1, MMP2 and MMP9) and CCND1 were used to explore the possible molecular mechanism of STX4 by which STX4 affects OC cells behavior, after which the effect of STX4 gene silencing on the proliferation of OC cells in vivo was tested.

RESULTS

After STX4 silencing, the biological behaviors of ovarian cancer cells including proliferation, migration and invasion, were significantly weakened. The results revealed that the E-cadherin, MMP2 and CCND1 levels of both OC cell lines were decreased after STX4 gene silencing. Animal models of STX4 gene silencing showed the tumorigenicity of tumor cells was reduced.

CONCLUSION

We demonstrated for the first time that STX4, an important regulator of OC progression, was associated with the growth and metastasis of OC cells through correlations with EMT, MMP2, and CCND1, suggesting its potential as a new therapeutic target for OC.