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Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells

Marine drugs, 2015-09, Vol.13 (10), p.6099-6116 [Peer Reviewed Journal]

Copyright MDPI AG 2015 ;2015 by the authors; licensee MDPI, Basel, Switzerland. 2015 ;ISSN: 1660-3397 ;EISSN: 1660-3397 ;DOI: 10.3390/md13106099 ;PMID: 26404322

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Title:
Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells
Author: Yan, Ming-De ; Yao, Chih-Jung ; Chow, Jyh-Ming ; Chang, Chia-Lun ; Hwang, Pai-An ; Chuang, Shuang-En ; Whang-Peng, Jacqueline ; Lai, Gi-Ming
Subjects: Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA Methyltransferase 3B ; DNMT3B ; Dose-Response Relationship, Drug ; Down-Regulation - drug effects ; EMT ; fucoidan ; Gene Expression Regulation, Neoplastic - drug effects ; hepatocellular carcinoma ; Humans ; Liver Neoplasms - drug therapy ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Marine ; Microfilament Proteins - genetics ; MicroRNAs - genetics ; miR-29b ; MTSS1 ; Neoplasm Proteins - genetics ; Polysaccharides - administration & dosage ; Polysaccharides - pharmacology ; Receptors, Transforming Growth Factor beta - metabolism ; RNA, Messenger - metabolism ; Signal Transduction - drug effects ; Transforming Growth Factor beta - metabolism ; Up-Regulation - drug effects
Is Part Of: Marine drugs, 2015-09, Vol.13 (10), p.6099-6116
Description: 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.
Publisher: Switzerland: MDPI AG
Language: English
Identifier: ISSN: 1660-3397
EISSN: 1660-3397
DOI: 10.3390/md13106099
PMID: 26404322
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
ROAD: Directory of Open Access Scholarly Resources
ProQuest Central
DOAJ Directory of Open Access Journals

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Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells

Copyright MDPI AG 2015 ;2015 by the authors; licensee MDPI, Basel, Switzerland. 2015 ;ISSN: 1660-3397 ;EISSN: 1660-3397 ;DOI: 10.3390/md13106099 ;PMID: 26404322

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