Expression Characteristics of KAI1 and Vascular Endothelial Growth Factor and Their Diagnostic Value for Hepatocellular Carcinoma

Wu, Zijian; Zhao, Cheng; Sun, Hong; Zheng, Wei; Chen, Hua

doi:10.5009/gnl13331

Cited by 10 publications

(5 citation statements)

References 22 publications

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“…In hepatocellular carcinoma, downregulation of Tspan27/CD82 and loss of Tspan28/CD81 was observed in poorly differentiated tumors . Interestingly, Tspan27 level correlated inversely with intrahepatic metastases but not with tumor size or expression of alpha‐fetoprotein . In contrast, increase of Tspan8/TM4SF3/CO‐029 expression was associated with poorly differentiated HCCs and intrahepatic spreading .…”

Section: Introductionmentioning

confidence: 99%

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

et al. 2019

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Hepatocellular carcinoma (HCC) is the second cause of cancer‐related deaths worldwide. A clearer understanding of the molecular mechanisms underlying tumor growth and invasiveness remains crucial for developing new therapies. Here, the expression of tetraspanins, a family of plasma membrane organizers involved in tumor progression, has been addressed. Integrative approaches combining transcriptomics and bioinformatics allow demonstrating the induced and heterogeneous expression of Tspan15 in HCC. Tspan15 positive tumors exhibit signatures related to hepatic progenitor cells as well as recurrence of cancer. Immunohistochemistry experiments confirm Tspan15 expression in the subset of HCC expressing stemness‐related markers such as EpCAM and Cytokeratin‐19. Functional networks reveal that most of these genes expressed in correlation to Tspan15 support cell proliferation. Furthermore, Tspan15 overexpression in the hepatoma cell line HepG2 significantly increases cell proliferation. A quantitative proteomic analysis of the secretome reveals a higher abundance of the protein connective tissue growth factor (CTGF), a pleiotropic matricellular signaling protein. Proteomic profiling of Tspan15 complexes allows identifying numerous membrane proteins including several growth factor receptors. Finally, Tspan15 increases ERK1/2 phosphorylation that directly controls CTGF expression and secretion. In conclusion, Tspan15 is a new stemness‐related marker in HCC which exhibits high potential of tumor growth and recurrence.

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Section: Introductionmentioning

confidence: 99%

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

et al. 2019

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“…HBV has been found to inhibit KAI1 by hypermethylation of KAI1 promoter, which maybe a key step in hepatocellular carcinoma progression (13). In addition, there exists a correlation between KAI1 and VEGF expression in the serum or tissue sample in HCC patients (14). The inhibition of KAI1 was related to EGFR over-expression, as well as EGFR mutations in non-small cell lung cancers (15).…”

Section: Introductionmentioning

confidence: 99%

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

et al. 2016

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Background:The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in malignant progression of lung cancer. However, the underlying mechanism of anti-metastasis role of KAI1 in lung cancer is hardly known. In this paper, we sought to study the function and regulatory mechanism of KAI1 in high metastasis lung cancer cell line.Methods: KAI1 expression was detected in high/low metastatic large lung cancer cell line L9981/NL9980 by quantitative real-time polymerase chain reaction (qRT-PCR). The tumor suppressor function of KAI1 was determined by wound healing assay after over-expression or knockdown of KAI1 in L9981 or NL9980 cells.Invasion assay was performed to detect the invasion ability of L9981 by transfection of KAI1. The effect of tumor suppressor p53 on KAI1 expression was measured by western blot and luciferase assay. Then the regulation of KAI1 due to over-expression of metastasis suppressor nm23-H1 was monitored by qRT-PCR, western blot and reporter gene assay. The progression of L9981 cells after p53 and nm23-H1 expression was detected by invasion assay. Also, methylation status of KAI1 promoter in NL9980 and L9981 cells were examined by bisulfite sequencing and methylation-specific PCR.Results: We found that KAI1 is down-regulated in high metastatic L9981 cells compare with NL9980 cells. The migration and invasion of L9981 cells were remarkably suppressed in vitro by KAI1 transfection.The migration ability of NL9980 was enhanced by inhibition of KAI1. Furthermore, KAI1 expression was induced after over-expression of p53 or nm23-H1, while cell invasion was inhibited in L9981 cells. The results of reporter analysis indicated that KAI1 promoter region between −922 to −846 could response to nm23-H1. In addition, we discovered only slight methylation of KAI1 promoter, which showed that loss expression of KAI1 in L9981 cells may not due to promoter methylation. Conclusions:The results suggested that nm23-H1 was involved in the KAI1-regulated inhibition of metastasis in lung cancer cells. More insights into the relationship between KAI1 and other metastasis suppressors will pave the way for the elucidation of anti-metastasis mechanism in lung cancer.

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“…CD82 protein was present in about one-third of colorectal cancer tissues compared with more than half of normal mucosal tissues (34). In addition, its expression was lower in hepatocellular malignant cells compared with healthy tissue (35) and in HCC patients compared with patients with liver cirrhosis or hepatitis, or control individuals (35). Taking all this into account, our finding that a variant located in CD82 gene was significantly associated with NAFLD might explain the increased risk of several malignancies in patients with NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Association between rs2303861 polymorphism in CD82 gene and non-alcoholic fatty liver disease: a preliminary case-control study

Habibzadeh

Honarvar

Silawi³

et al. 2019

Croat Med J

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AimTo investigate the genetic factors involved in the development of non-alcoholic fatty liver disease (NAFLD) and its sequelae in a Middle Eastern population.MethodsThis genetic case-control association study, conducted in 2018, enrolled 30 patients with NAFLD and 30 control individuals matched for age, sex, and body mass index. After quality control measures, entire exonic regions of 3654 genes associated with human diseases were sequenced. Allelic association test and enrichment analysis of the significant genetic variants were performed.ResultsThe association analysis was conducted on 27 NAFLD patients and 28 controls. When Bonferroni correction was applied, NAFLD was significantly associated with rs2303861, a variant located in the CD82 gene (P = 2.49 × 10−7, adjusted P = 0.0059). When we used Benjamini-Hochberg adjustment for correction, NAFLD was significantly associated with six more variants. Enrichment analysis of the genes corresponding to all the seven variants showed significant enrichment for miR-193b-5p (P = 0.00004, adjusted P = 0.00922).ConclusionA variant on CD82 gene and a miR-193b expression dysregulation may have a role in the development and progression of NAFLD and its sequelae.

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Expression Characteristics of KAI1 and Vascular Endothelial Growth Factor and Their Diagnostic Value for Hepatocellular Carcinoma

Cited by 10 publications

References 22 publications

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

Association between rs2303861 polymorphism in CD82 gene and non-alcoholic fatty liver disease: a preliminary case-control study

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