Expression of combined interference of slug and FoxC2 in endometrial carcinoma and its clinicopathological relationship

Qing Zhu; Mingyang Tang; Ligao Wu

doi:10.21037/tcr-20-809

Expression of combined interference of slug and FoxC2 in endometrial carcinoma and its clinicopathological relationship

Transl Cancer Res. 2020 Sep;9(9):5268-5280. doi: 10.21037/tcr-20-809.

Authors

Qing Zhu^#^{1

2}, Mingyang Tang³, Ligao Wu^#^{1

2}

Affiliations

¹ Departments of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
² Department of Pathology, Bengbu Medical College, Bengbu, China.
³ Clinical Medicine Science, School of Clinical Medicine, Bengbu Medical College, Bengbu, China.

^# Contributed equally.

Abstract

Background: Endometrial carcinoma is one of the three major malignant tumors in female reproductive system. The current research aimed to investigate the relationship between the Slug and FoxC2 expression and the proliferation, invasion and metastasis of endometrial carcinoma.

Methods: The expression of Slug and FoxC2 genes between 124 endometrial carcinoma tissues and 35 normal endometrial tissues was analyzed through immunohistochemistry. The endometrial carcinoma cell lines Ishikawa and RL-952 were cultured, the Slug-shRNA and FoxC2-shRNA expression vectors were constructed, and the endometrial carcinoma cells interfering with the expression of Slug and FoxC2 genes were also established. Western blotting and RT-PCR were employed to verify whether shRNA could down regulate the expression of Slug and FoxC2 genes. Additionally, the proliferation, migration and invasion capacities in both cell lines after interfering with Slug and FoxC2 was detected through CCK-8 and Transwell assay respectively. Furthermore, MMP2 and MMP9 were detected by ELISA and epithelial-mesenchymal transition (EMT) related proteins including E-cadherin, N-cadherin and Vimentin were assessed by Western blotting analysis.

Results: Compared with normal endometrial tissues, the Slug and FoxC2 expression levels in endometrial carcinoma tissues were remarkably increased. shRNAs transfection significantly down-regulated expressions in both endometrial carcinoma cell lines. The proliferation, invasion and migration ability were significantly inhibited by Slug-shRNA and FoxC2-shRNA compared with the control group. The expression of E-cadherin was increased while the expression of N-cadherin, Vimentin, MMP-2 and MMP-9 was suppressed by the Slug-shRNA and FoxC2-shRNA.

Conclusions: Slug and FoxC2 could be used as a prognostic factor of endometrial carcinoma. Interfering with the expression of Slug and FoxC2 in endometrial carcinoma cell lines could effectively inhibit the proliferation, invasion and migration, and its mechanism is related to the inhibition of EMT. Slug and FoxC2 are potential targets for the treatment of endometrial carcinoma.

Keywords: Endometrial carcinoma; FoxC2; Slug; epithelial-mesenchymal transition (EMT); gene targeting regulation.