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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 3/2016

01-03-2016 | Research Paper

A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells

Authors: Shiro Kohi, Norihiro Sato, Xiao-Bo Cheng, Atsuhiro Koga, Aiichiro Higure, Keiji Hirata

Published in: Clinical & Experimental Metastasis | Issue 3/2016

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma enriched with hyaluronan (HA), a major component of extracellular matrix known to play a critical role in tumor progression. The mechanisms that regulate HA synthesis in PDAC are poorly understood. To investigate whether DNA methylation and HA production from PDAC cells are associated, we studied the effect of 5-aza-2′-deoxycitidine (5-aza-dC), an inhibitor of DNA methylation, or DNA methyltransferase 1 (DNMT1) knockdown by small interfering RNA, on the HA production from PDAC cells. HA production into the conditioned medium was evaluated in PDAC cells treated with 5-aza-dC or DNMT1 knockdown. mRNA expression of HA synthase (HAS) genes was investigated by real-time RT-PCR. Treatment of PDAC cells with 5-aza-dC led to a significant increase in the HA production (up to 2.5-fold increase) in all 4 cell lines tested. This enhanced HA production by 5-aza-dC treatment was accompanied by increased mRNA expression of HAS2 and HAS3. Furthermore, increased HA production and HAS2/HAS3 mRNA expression was also observed in PDAC cells by knockdown of DNMT1. These findings provide evidence, for the first time, that epigenetic mechanism is involved in the regulation of HA synthesis in PDAC cells.
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Metadata
Title
A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells
Authors
Shiro Kohi
Norihiro Sato
Xiao-Bo Cheng
Atsuhiro Koga
Aiichiro Higure
Keiji Hirata
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 3/2016
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-015-9771-9

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