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KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) has very high prevalence and associated-mortality. However, targeted therapies that are currently used in clinical practice for HCC have certain limitations, in part because of the lack of reliable and clinically applicable biomarkers that can be used for d...

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Autores principales: Shi, Lei, Zhang, Wenfa, Zou, Fagui, Mei, Lihua, Wu, Gang, Teng, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073891/
https://www.ncbi.nlm.nih.gov/pubmed/27769251
http://dx.doi.org/10.1186/s12885-016-2851-7
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author Shi, Lei
Zhang, Wenfa
Zou, Fagui
Mei, Lihua
Wu, Gang
Teng, Yong
author_facet Shi, Lei
Zhang, Wenfa
Zou, Fagui
Mei, Lihua
Wu, Gang
Teng, Yong
author_sort Shi, Lei
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) has very high prevalence and associated-mortality. However, targeted therapies that are currently used in clinical practice for HCC have certain limitations, in part because of the lack of reliable and clinically applicable biomarkers that can be used for diagnosis and prognosis assessments and for the surveillance of treatment effectiveness. METHODS: Meta-analysis was used to analyze the integrated microarray data for global identification of a set of robust biomarkers for HCC. Quantitative RT-PCR (qRT-PCR) was performed to validate the expression levels of selected genes. Gene expression was inhibited by siRNA. CellTiter 96(®) AQueous One Solution Cell Proliferation assays were used to determine cell proliferation, and Transwell assays were used to determine cell migration and invasion potential. RESULTS: Meta-analysis of the expression data provided a gene expression signature from a total of 1525 patients with HCC, showing 1529 up-regulated genes and 478 down-regulated genes in cancer samples. The expression levels of genes having strong clinical significance were validated by qRT-PCR using primary HCC tissues and the paired adjacent noncancerous liver tissues. Up-regulation of VPS45, WIPI1, TTC1, IGBP1 and KLHL21 genes and down-regulation of FCGRT gene were confirmed in clinical HCC samples. KLHL21 was the most promising gene for potential use as a bioclinical marker in this analysis. Abrogating expression of it significantly inhibited cell proliferation, migration and invasion. CONCLUSIONS: Our study suggests that KLHL21 is a potential target for therapeutic intervention. Our findings also provide novel candidate genes on a genome-wide scale, which may have significant impact on the design and execution of effective therapy of HCC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2851-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-50738912016-10-26 KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma Shi, Lei Zhang, Wenfa Zou, Fagui Mei, Lihua Wu, Gang Teng, Yong BMC Cancer Research Article BACKGROUND: Hepatocellular carcinoma (HCC) has very high prevalence and associated-mortality. However, targeted therapies that are currently used in clinical practice for HCC have certain limitations, in part because of the lack of reliable and clinically applicable biomarkers that can be used for diagnosis and prognosis assessments and for the surveillance of treatment effectiveness. METHODS: Meta-analysis was used to analyze the integrated microarray data for global identification of a set of robust biomarkers for HCC. Quantitative RT-PCR (qRT-PCR) was performed to validate the expression levels of selected genes. Gene expression was inhibited by siRNA. CellTiter 96(®) AQueous One Solution Cell Proliferation assays were used to determine cell proliferation, and Transwell assays were used to determine cell migration and invasion potential. RESULTS: Meta-analysis of the expression data provided a gene expression signature from a total of 1525 patients with HCC, showing 1529 up-regulated genes and 478 down-regulated genes in cancer samples. The expression levels of genes having strong clinical significance were validated by qRT-PCR using primary HCC tissues and the paired adjacent noncancerous liver tissues. Up-regulation of VPS45, WIPI1, TTC1, IGBP1 and KLHL21 genes and down-regulation of FCGRT gene were confirmed in clinical HCC samples. KLHL21 was the most promising gene for potential use as a bioclinical marker in this analysis. Abrogating expression of it significantly inhibited cell proliferation, migration and invasion. CONCLUSIONS: Our study suggests that KLHL21 is a potential target for therapeutic intervention. Our findings also provide novel candidate genes on a genome-wide scale, which may have significant impact on the design and execution of effective therapy of HCC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2851-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-21 /pmc/articles/PMC5073891/ /pubmed/27769251 http://dx.doi.org/10.1186/s12885-016-2851-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Shi, Lei
Zhang, Wenfa
Zou, Fagui
Mei, Lihua
Wu, Gang
Teng, Yong
KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma
title KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma
title_full KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma
title_fullStr KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma
title_full_unstemmed KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma
title_short KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma
title_sort klhl21, a novel gene that contributes to the progression of hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073891/
https://www.ncbi.nlm.nih.gov/pubmed/27769251
http://dx.doi.org/10.1186/s12885-016-2851-7
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