title: KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: School of Life Sciences, Chongqing University, Chongqing, 400044, People's Republic of China. shil@cqu.edu.cn.
authors: Lei
authors: L
authors: Shi
authors: School of Life Sciences, Chongqing University, Chongqing, 400044, People's Republic of China.
authors: Wenfa
authors: W
authors: Zhang
authors: School of Life Sciences, Chongqing University, Chongqing, 400044, People's Republic of China.
authors: Fagui
authors: F
authors: Zou
authors: School of Life Sciences, Chongqing University, Chongqing, 400044, People's Republic of China.
authors: Lihua
authors: L
authors: Mei
authors: Third Affiliated Hospital, Third Military Medical University, Chongqing, 400044, People's Republic of China.
authors: Gang
authors: G
authors: Wu
authors: Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, 30912, USA. yteng@augusta.edu.|GRU Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA. yteng@augusta.edu.|Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA. yteng@augusta.edu.
authors: Yong
authors: Y
authors: Teng
mesh_terms: D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Bioinformatics; Biomarker; HCC; KLHL21