Synaptotagmin-like protein 2 gene promotes the metastatic potential in ovarian cancer

Hye Youn Sung, Jihye Han, Woong Ju, Jung Hyuck Ahn

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Ovarian cancer (OC) metastasis has unique biological behavior and most commonly occurs via the transcoelomic route. Previously, we established a mouse xenograft model of human ovarian carcinoma and analyzed alterations in gene expression during metastasis. Among the genes that were differentially expressed more than 2-fold in the xenografts compared with the SK-OV-3 cells, we selected synaptotagmin-like protein 2 (SYTL2) and investigated the mechanisms regulating its expression and its gene function in OC. The mRNA expression of SYTL2 was significantly upregulated and the methylation of specific CpG sites within the SYTL2 promoter was decreased in the metastatic implants from the ovarian carcinoma xenografts compared to wild-type SK-OV-3 cells. Treatment with the demethylating agent 5-aza?2′-deoxycytidine and/or the histone deacetylase inhibitor Trichostatin A induced upregulation of SYTL2 in SK-OV-3 cells, implying that a DNA methylation-dependent epigenetic mechanism is involved in the regulation of SYTL2 expression. We also found that overexpression of SYTL2 promoted metastatic potential, including increased migration and invasiveness in the ovarian carcinoma cells. Furthermore, we utilized publicly available gene expression data to confirm the correlation between SYTL2 expression and poor prognosis in serous-type OC patients. Our findings provide novel evidence for the direct association of SYTL2 with the metastatic potential of ovarian carcinoma cells and its influence on metastatic recurrence of OC.

Original languageEnglish
Pages (from-to)535-541
Number of pages7
JournalOncology Reports
Volume36
Issue number1
DOIs
StatePublished - Jul 2016

Bibliographical note

Publisher Copyright:
© 2016, Spandidos Publications. All rights reserved.

Keywords

  • DNA methylation
  • Metastasis
  • Ovarian cancer
  • Synaptotagmin-like protein 2

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