KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma?a functional analysis

Lei, Z. H.; Qin, Lun–Xiu; Ye, Qing–Hai; Zhu, Xiao-Qun; Zhang, Hui; Wu, Xin; Chen, Jie; Liu, Yinkun; Tang, Zhao–You

doi:10.1007/s00432-004-0595-2

Cited by 18 publications

(13 citation statements)

References 22 publications

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“…This finding strongly supports the data from Kuo et al and Zhao et al, which showed that DLGAP5 is a potential oncogene that promotes the proliferation of HCC cells [21,25]. …”

Section: Discussionsupporting

confidence: 92%

Silencing of DLGAP5 by siRNA Significantly Inhibits the Proliferation and Invasion of Hepatocellular Carcinoma Cells

et al. 2013

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BackgroundThe dysregulation of oncogenes and tumor suppressor genes plays an important role in many cancers, including hepatocellular carcinoma (HCC), which is one of the most common cancers in the world. In a previous microarray experiment, we found that DLGAP5 is overexpressed in HCCs. However, whether the up-regulation of DLGAP5 contributes to hepatocarcinogenesis remains unclear. Methodology/Principal FindingsIn this study, we showed that DLGAP5 was significantly up-regulated in 76.4% (168 of 220) of the analyzed HCC specimens when compared with adjacent liver tissue. DLGAP5 overexpression was evident in 25% (22 of 88) of the HCC specimens without AFP expression, suggesting that DLGAP5 may be a novel biomarker for HCC pathogenesis. The silencing of DLGAP5 gene expression by RNA interference significantly suppressed cell growth, migration and colony formation in vitro. The expression level of DLGAP5 was also found to be related to the methylation level of its promoter in the HCC specimens. Conclusions/SignificanceTaken together, these data suggest that the expression of DLGAP5 is regulated by methylation and that the up-regulation of DLGAP5 contributes to HCC tumorigenesis by promoting cell proliferation.

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“…This finding strongly supports the data from Kuo et al and Zhao et al, which showed that DLGAP5 is a potential oncogene that promotes the proliferation of HCC cells [21,25]. …”

Section: Discussionsupporting

confidence: 92%

Silencing of DLGAP5 by siRNA Significantly Inhibits the Proliferation and Invasion of Hepatocellular Carcinoma Cells

et al. 2013

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“…The DLGAP5 gene encodes a cell-cycle-regulated, microtubule-associated protein known as DLG7, DAP-5 or HURP [34] that acts as a Ran GTPase effector involved in stabilization of the mitotic kinetochore fiber [35]. In hepatocellular carcinoma [36], meningioma [37] and adrenocortical tumors [38] the levels of transcripts encoding DLG7 increased with disease aggressiveness. These transcripts were detected in liver and colon tumors, but not in normal adjacent tissues suggesting an association of DLG7 and carcinogenesis [39,40].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Discs Large Homolog 7 Transcript Levels in Prostate Cancer

et al. 2013

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Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia–regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p≤0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP.

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“…(12,13) Progress in basic scientific research has led to a better understanding of molecular mechanism responsible for HCC (12)(13)(14)(15). For example, altered DNA methylation, genomic alterations (13,14) (16,17) and many deregulated genes such as HBx, TP53, IGF2, CDKN2A (p16 INK4A ), RB1, PTEN, DLC1, MMP, APC, CTNNB1, and AXIN1 (12)(13)(14)(15)18) may play roles in development of HCC. Biological pathways such as upregulation of mitogenic pathways, MAPK/ERK, ras/raf/MAPK, NF κ -B, ERBB2/NEU, JAK/STAT, and Wnt/β-catenin signal transduction pathways (14) have been found to be altered in HCC.…”

Section: Introductionmentioning

confidence: 99%

System biology analysis of cell cycle pathway involved in hepatocellular carcinoma

Sun

Mo²,

Fu³

et al. 2010

Front Biosci

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To investigate genetic mechanisms of hepatocarcinogenesis and identify potential anticancer targets in hepatocellular carcinoma (HCC), we analyzed microarray gene expression profiles between 33 HCCs and their corresponding noncancerous liver tissues. Functional analysis of differentially-expressed genes in HCC indicated that cell cycle dysregulation plays an important role in hepatocarcinogenesis. Based on 14 differentially-expressed genes involved in cell cycle in HCC, we applied Structural Equation Modeling (SEM) to establish a potential genetic network which could assist understanding of HCC molecular mechanisms. siRNA-mediated knock-down of two significantly up-regulated genes, minichromosome maintenance protein 2 (MCM2) and cyclin B1 (CCNB1), in HCC cells (SMMC-7721 and QGY-7703) induced G2/M-phase arrest, apoptosis and antiproliferation in HCC. Some up-regulated cell cycle-related genes in HCC were down-regulated following specific depletion of MCM2 or/and CCNB1 in HCC cells, which might well validate and complement the reconstructed cell cycle network. This study may contribute to further disclose hepatocarcinogenesis mechanism through systematically analyzed the HCC-related-cell-cycle pathway. This study also shows that MCM2 and CCNB1 could be promising prognostic and therapeutic targets for HCC.

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KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma?a functional analysis

Abstract: KIAA0008 expression is associated with invasiveness of HCC; overexpression of KIAA0008 leads to a more invasive phenotype of HCC cell lines.

Cited by 18 publications

References 22 publications

Silencing of DLGAP5 by siRNA Significantly Inhibits the Proliferation and Invasion of Hepatocellular Carcinoma Cells

Silencing of DLGAP5 by siRNA Significantly Inhibits the Proliferation and Invasion of Hepatocellular Carcinoma Cells

Prognostic Value of Discs Large Homolog 7 Transcript Levels in Prostate Cancer

System biology analysis of cell cycle pathway involved in hepatocellular carcinoma

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