A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells

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...

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Bibliographic Details
Published in:Clinical & experimental metastasis 2016-03, Vol.33 (3), p.225-230
Main Authors: Kohi, Shiro, Sato, Norihiro, Cheng, Xiao-Bo, Koga, Atsuhiro, Higure, Aiichiro, Hirata, Keiji
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Cell Line, Tumor
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic - genetics
Glucuronosyltransferase - analysis
Glucuronosyltransferase - biosynthesis
Hematology
Humans
Hyaluronan Synthases
Hyaluronic Acid - biosynthesis
Oncology
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Real-Time Polymerase Chain Reaction
Research Paper
RNA, Messenger - analysis
Surgical Oncology
Transcriptome
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Summary: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.
ISSN:0262-0898
1573-7276
DOI:10.1007/s10585-015-9771-9