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

Lei Shi, Wenfa Zhang, Fagui Zou, Lihua Mei, Gang Wu, Yong Teng

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number815
JournalBMC Cancer
Volume16
Issue number1
DOIs
StatePublished - Oct 21 2016

Fingerprint

Hepatocellular Carcinoma
Genes
Cell Proliferation
Cell Movement
Meta-Analysis
Biomarkers
Gene Expression
Polymerase Chain Reaction
Neoplasm Genes
Microarray Analysis
Transcriptome
Small Interfering RNA
Up-Regulation
Therapeutics
Down-Regulation
Genome
Mortality
Liver

Keywords

  • Bioinformatics
  • Biomarker
  • HCC
  • KLHL21

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma. / Shi, Lei; Zhang, Wenfa; Zou, Fagui; Mei, Lihua; Wu, Gang; Teng, Yong.

In: BMC Cancer, Vol. 16, No. 1, 815, 21.10.2016.

Research output: Contribution to journalArticle

Shi, Lei ; Zhang, Wenfa ; Zou, Fagui ; Mei, Lihua ; Wu, Gang ; Teng, Yong. / KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma. In: BMC Cancer. 2016 ; Vol. 16, No. 1.
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AB - 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.

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