Downregulation of nicotinamide N-methyltransferase inhibits migration and epithelial-mesenchymal transition of esophageal squamous cell carcinoma via Wnt/β-catenin pathway

Yanyan Cui, Luyu Zhang, Wenjie Wang, Shanshan Ma, Hongtao Liu, Xingxing Zang, Yanting Zhang, Fangxia Guan

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Nicotinamide N-methyltransferase (NNMT) is an important methyltransferase involved in the biotransformation of many drugs and exogenous compounds. Abnormal expression of NNMT protein is closely associated with the onset and progression of many malignancies, but little is known about its role in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to explore whether NNMT plays any roles in carcinogenesis and metastasis in ESCC. NNMT expression was determined by immunohistochemistry in ESCC and corresponding adjacent normal tissues. Functional experiments were performed to elucidate the effects of NNMT knockdown on the proliferation, apoptosis, cell cycle, migration, and epithelial-mesenchymal transition (EMT) in EC9706 and TE1 cells. NNMT expression was significantly elevated in ESCC tissues compared with corresponding adjacent normal tissues. Moreover, a significant association emerged between NNMT expression and lymph node metastasis. SiRNA-mediated knockdown of NNMT in ESCC cells can significantly suppress cell viability and migration, induce cell cycle arrest, and promote cell apoptosis. In addition, NNMT downregulation led to the reversal of EMT, as reflected by upregulation of the intercellular adhesion molecule E-cadherin and downregulation of the mesenchymal markers N-cadherin and Vimentin. Further study found that NNMT knockdown suppressed the Wnt/β-catenin signaling pathway. Taken together, these findings indicate that NNMT is a critical regulator of EMT in ESCC and may be a potential therapeutic target for ESCC metastasis.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume460
Issue number1-2
DOIs
StatePublished - Oct 1 2019

Keywords

  • Epithelial-mesenchymal transition (EMT)
  • Esophageal squamous cell carcinoma (ESCC)
  • Metastasis
  • Nicotinamide N-methyltransferase (NNMT)
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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