Fucoidan elevates MicroRNA-29b to regulate DNMT3B-MTSS1 axis and inhibit EMT in human hepatocellular carcinoma cells

Ming De Yan, Chih Jung Yao, Jyh Ming Chow, Chia Lun Chang, Pai An Hwang, Shuang En Chuang, Jacqueline Whang-Peng, Gi Ming Lai

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Accumulating evidence has revealed that fucoidan exhibits anti-tumor activities by arresting cell cycle and inducing apoptosis in many types of cancer cells including hepatocellular carcinoma (HCC). Exploring its effect on microRNA expression, we found that fucoidan markedly upregulated miR-29b of human HCC cells. The induction of miR-29b was accompanied with suppression of its downstream target DNMT3B in a dose-dependent manner. The reduction of luciferase activity of DNMT3B 3′-UTR reporter by fucoidan was as markedly as that by miR-29b mimic, indicating that fucoidan induced miR-29b to suppress DNMT3B. Accordingly, the mRNA and protein levels of MTSS1 (metastasis suppressor 1), a target silenced by DNMT3B, were increased after fucoidan treatment. Furthermore, fucoidan also down-regulated TGF-β receptor and Smad signaling of HCC cells. All these effects leaded to the inhibition of EMT (increased E-cadherin and decreased N-cadherin) and prevention of extracellular matrix degradation (increased TIMP-1 and decreased MMP2, 9), by which the invasion activity of HCC cells was diminished. Our results demonstrate the profound effect of fucoidan not only on the regulation of miR-29b-DNMT3B-MTSS1 axis but also on the inhibition of TGF-β signaling in HCC cells, suggesting the potential of using fucoidan as integrative therapeutics against invasion and metastasis of HCC.

Original languageEnglish
Pages (from-to)6099-6116
Number of pages18
JournalMarine Drugs
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • DNMT3B
  • EMT
  • Fucoidan
  • Hepatocellular carcinoma
  • MiR-29b
  • MTSS1

ASJC Scopus subject areas

  • Drug Discovery

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