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Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion

BACKGROUND: Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199...

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Autores principales: Shen, Qingli, Cicinnati, Vito R, Zhang, Xiaoyong, Iacob, Speranta, Weber, Frank, Sotiropoulos, Georgios C, Radtke, Arnold, Lu, Mengji, Paul, Andreas, Gerken, Guido, Beckebaum, Susanne
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939569/
https://www.ncbi.nlm.nih.gov/pubmed/20799954
http://dx.doi.org/10.1186/1476-4598-9-227
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author Shen, Qingli
Cicinnati, Vito R
Zhang, Xiaoyong
Iacob, Speranta
Weber, Frank
Sotiropoulos, Georgios C
Radtke, Arnold
Lu, Mengji
Paul, Andreas
Gerken, Guido
Beckebaum, Susanne
author_facet Shen, Qingli
Cicinnati, Vito R
Zhang, Xiaoyong
Iacob, Speranta
Weber, Frank
Sotiropoulos, Georgios C
Radtke, Arnold
Lu, Mengji
Paul, Andreas
Gerken, Guido
Beckebaum, Susanne
author_sort Shen, Qingli
collection PubMed
description BACKGROUND: Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. METHODS: Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis. RESULTS: A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. CONCLUSIONS: Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.
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spelling pubmed-29395692010-09-16 Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion Shen, Qingli Cicinnati, Vito R Zhang, Xiaoyong Iacob, Speranta Weber, Frank Sotiropoulos, Georgios C Radtke, Arnold Lu, Mengji Paul, Andreas Gerken, Guido Beckebaum, Susanne Mol Cancer Research BACKGROUND: Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. METHODS: Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis. RESULTS: A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. CONCLUSIONS: Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC. BioMed Central 2010-08-27 /pmc/articles/PMC2939569/ /pubmed/20799954 http://dx.doi.org/10.1186/1476-4598-9-227 Text en Copyright ©2010 Shen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Shen, Qingli
Cicinnati, Vito R
Zhang, Xiaoyong
Iacob, Speranta
Weber, Frank
Sotiropoulos, Georgios C
Radtke, Arnold
Lu, Mengji
Paul, Andreas
Gerken, Guido
Beckebaum, Susanne
Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
title Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
title_full Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
title_fullStr Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
title_full_unstemmed Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
title_short Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
title_sort role of microrna-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939569/
https://www.ncbi.nlm.nih.gov/pubmed/20799954
http://dx.doi.org/10.1186/1476-4598-9-227
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