Epigenetic inactivation of SPINT2 is associated with tumor suppressive function in esophageal squamous cell carcinoma

Dongli Yue, Qingxia Fan, Xinfeng Chen, Feng Li, Liping Wang, Lan Huang, Wenjie Dong, Xiaoqi Chen, Zhen Zhang, Jinyan Liu, Fei Wang, Meng Wang, Bin Zhang, Yi Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Hepatocyte growth factor activator inhibitor type 2 (SPINT2), a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor suppressor gene silenced by promoter methylation. We aimed to investigate whether SPINT2 might act as an esophageal squamous cell carcinoma (ESCC) tumor suppressor gene. Four ESCC cell lines, Fifty-two ESCC tissues and twenty-nine neighboring non-cancerous tissues were included in this study. The expression of SPINT2 was monitored by real time PCR. Bisulfite genomic sequencing and methylation-specific PCR were used to analyze methylation status. The effect of SPINT2 on cell proliferation and apoptosis in EC109 and EC9706 cells was observed by CCK-8 assay and flow cytometric analysis. We found that silencing of SPINT2 was associated with promoter methylation in ESCC cell lines. The densely methylated SPINT2 promoter region was confirmed by bisulfite genomic sequencing. Ectopic expression of SPINT2 inhibited cell proliferation through inducing cell apoptosis in vitro. Furthermore, methylation-specific PCR analysis revealed that SPINT2 promoter methylation was prominent in carcinoma tissues (52.08%) compared with neighboring non-cancerous tissues (22.58%). Kaplan-Meier analysis showed that patients with SPINT2 hypermethylation had shorter survival time. The tumor suppressor gene of SPINT2 is commonly silenced by promoter hypermethylation in human ESCC and SPINT2 hypermethylation is correlated with poor overall survival, implicating SPINT2 is an underlying prognostic marker for human ESCC.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalExperimental Cell Research
Volume322
Issue number1
DOIs
StatePublished - Mar 10 2014

Keywords

  • Esophageal squamous cell carcinoma (ESCC)
  • Methylation
  • SPINT2

ASJC Scopus subject areas

  • Cell Biology

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