Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.

<h4>Background</h4>Hepatocellular carcinoma (HCC) is a classical example of inflammation-linked cancer and is characterized by hypervascularity suggesting rich angiogenesis. Cycloxygenase-2 (COX-2) is a potent mediator of inflammation and is considered to upregulate angiogenesis. The aim...

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Main Authors: Wenjiao Zeng, Anke van den Berg, Sippie Huitema, Annette S H Gouw, Grietje Molema, Koert P de Jong
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24759835/pdf/?tool=EBI
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spelling doaj-793eb55b552845a4adb4c6d79aeb4c1f2021-03-04T09:30:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9582610.1371/journal.pone.0095826Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.Wenjiao ZengAnke van den BergSippie HuitemaAnnette S H GouwGrietje MolemaKoert P de Jong<h4>Background</h4>Hepatocellular carcinoma (HCC) is a classical example of inflammation-linked cancer and is characterized by hypervascularity suggesting rich angiogenesis. Cycloxygenase-2 (COX-2) is a potent mediator of inflammation and is considered to upregulate angiogenesis. The aims of the study are (1) to analyze expression of Cox-2 mRNA, Cox-2 protein, miR-16, miR-21 and miR-101 in HCC and adjacent liver parenchyma in cirrhotic and noncirrhotic liver, (2) to investigate the relation between COX-2 expression, miR-21 expression and angiogenic factors in these tissues and (3) to investigate the association between miR-16 and miR-101 and COX-2 expression.<h4>Methods</h4>Tissue samples of HCC and adjacent liver parenchyma of 21 noncirrhotic livers and 20 cirrhotic livers were analyzed for COX-2 expression at the mRNA level (qRT-PCR) and at the protein level by Western blot and immunohistochemistry. Gene expression of VEGFA, VEGFR1, VEGFR2, Ang-1, Ang-2 and Tie-2 were correlated with COX-2 levels. miR-16, miR-21 and miR-101 gene expression levels were quantified in HCC tumor tissue.<h4>Results</h4>COX-2 mRNA and protein levels were lower in HCC as compared to adjacent liver parenchyma both in cirrhotic and noncirrhotic liver. COX-2 protein localized mainly in vascular and sinusoidal endothelial cells and in Kupffer cells. At the mRNA level but not at the protein level, COX-2 correlated with mRNA levels of angiogenic factors VEGFR1, Ang-1, and Tie2. miR-21 expression was higher in cirrhotic tissues versus noncirrhotic tissues. MiR-101 expression was lower in cirrhotic versus noncirrhotic adjacent liver parenchyma. None of the miRNAs correlelated with COX-2 expression. miR-21 correlated negatively with Tie-2 receptor in adjacent liver parenchyma.<h4>Conclusions</h4>In human HCC, COX-2 mRNA but not COX-2 protein levels are associated with expression levels of angiogenic factors. MiR-21 levels are not associated with angiogenic molecules. MiR-16 and miR-101 levels do not correlate with COX-2 mRNA and protein levels.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24759835/pdf/?tool=EBI
collection DOAJ
language English
format Article
sources DOAJ
author Wenjiao Zeng
Anke van den Berg
Sippie Huitema
Annette S H Gouw
Grietje Molema
Koert P de Jong
spellingShingle Wenjiao Zeng
Anke van den Berg
Sippie Huitema
Annette S H Gouw
Grietje Molema
Koert P de Jong
Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
PLoS ONE
author_facet Wenjiao Zeng
Anke van den Berg
Sippie Huitema
Annette S H Gouw
Grietje Molema
Koert P de Jong
author_sort Wenjiao Zeng
title Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
title_short Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
title_full Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
title_fullStr Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
title_full_unstemmed Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
title_sort correlation of microrna-16, microrna-21 and microrna-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description <h4>Background</h4>Hepatocellular carcinoma (HCC) is a classical example of inflammation-linked cancer and is characterized by hypervascularity suggesting rich angiogenesis. Cycloxygenase-2 (COX-2) is a potent mediator of inflammation and is considered to upregulate angiogenesis. The aims of the study are (1) to analyze expression of Cox-2 mRNA, Cox-2 protein, miR-16, miR-21 and miR-101 in HCC and adjacent liver parenchyma in cirrhotic and noncirrhotic liver, (2) to investigate the relation between COX-2 expression, miR-21 expression and angiogenic factors in these tissues and (3) to investigate the association between miR-16 and miR-101 and COX-2 expression.<h4>Methods</h4>Tissue samples of HCC and adjacent liver parenchyma of 21 noncirrhotic livers and 20 cirrhotic livers were analyzed for COX-2 expression at the mRNA level (qRT-PCR) and at the protein level by Western blot and immunohistochemistry. Gene expression of VEGFA, VEGFR1, VEGFR2, Ang-1, Ang-2 and Tie-2 were correlated with COX-2 levels. miR-16, miR-21 and miR-101 gene expression levels were quantified in HCC tumor tissue.<h4>Results</h4>COX-2 mRNA and protein levels were lower in HCC as compared to adjacent liver parenchyma both in cirrhotic and noncirrhotic liver. COX-2 protein localized mainly in vascular and sinusoidal endothelial cells and in Kupffer cells. At the mRNA level but not at the protein level, COX-2 correlated with mRNA levels of angiogenic factors VEGFR1, Ang-1, and Tie2. miR-21 expression was higher in cirrhotic tissues versus noncirrhotic tissues. MiR-101 expression was lower in cirrhotic versus noncirrhotic adjacent liver parenchyma. None of the miRNAs correlelated with COX-2 expression. miR-21 correlated negatively with Tie-2 receptor in adjacent liver parenchyma.<h4>Conclusions</h4>In human HCC, COX-2 mRNA but not COX-2 protein levels are associated with expression levels of angiogenic factors. MiR-21 levels are not associated with angiogenic molecules. MiR-16 and miR-101 levels do not correlate with COX-2 mRNA and protein levels.
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24759835/pdf/?tool=EBI
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