Related Experiment Video
Updated: Apr 3, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells
Ming-De Yan1, Chih-Jung Yao2,3,4, Jyh-Ming Chow5,6
1Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan. yanmd717@gmail.com.
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.
Insights
Fucoidan, a compound from seaweed, inhibits hepatocellular carcinoma (HCC) invasion by upregulating miR-29b, suppressing DNMT3B, and blocking TGF-β signaling pathways. This suggests fucoidan
Area of Science:
- Marine natural products
- Cancer biology
- Molecular oncology
Background:
- Fucoidan demonstrates anti-tumor properties in hepatocellular carcinoma (HCC).
- Fucoidan's impact on microRNA expression in HCC requires further elucidation.
- Understanding fucoidan's molecular mechanisms is crucial for therapeutic development.
Purpose of the Study:
- To investigate the effect of fucoidan on microRNA expression in HCC cells.
- To elucidate the molecular pathways targeted by fucoidan in HCC.
- To assess fucoidan's potential as an anti-metastatic agent for HCC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure microRNA and mRNA levels.
- Western blotting to assess protein expression.
- Luciferase reporter assays to confirm target gene regulation.
- Cell-based assays to evaluate epithelial-mesenchymal transition (EMT) and invasion.
Main Results:
- Fucoidan significantly upregulated miR-29b in HCC cells, dose-dependently suppressing its target DNMT3B.
- Fucoidan treatment increased MTSS1 expression, a DNMT3B target, and downregulated TGF-β receptor and Smad signaling.
- Fucoidan inhibited EMT, reduced extracellular matrix degradation, and diminished HCC cell invasion.
Conclusions:
- Fucoidan regulates the miR-29b-DNMT3B-MTSS1 axis and inhibits TGF-β signaling in HCC.
- Fucoidan demonstrates significant anti-invasive and anti-metastatic potential in HCC.
- Fucoidan may serve as an integrative therapeutic agent for managing HCC invasion and metastasis.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs
01:15Drugs that Stabilize Microtubules