HDGF-related protein-3 is required for anchorage-independent survival and chemoresistance in hepatocellular carcinomas

Xiao, Qianyi; Qu, Kai; Wang, Chenji; Kong, Yahui; Liu, Chao; Jiang, Deke; Saiyin, Hexige; Fan, Jia; Chen, Ni; Chen, Taoyang; Zhang, Yuanyuan; Zhang, Pingzhao; Qin, Wenxin; Sun, Qingwen; Wang, Hongyang; Yi, Qing; Li, Jun; Huang, Haojie; Liu, Yu

doi:10.1136/gutjnl-2011-300781

Cited by 33 publications

(28 citation statements)

References 33 publications

(30 reference statements)

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“…Based on several in vitro trials involving recombinant proteins (30) and the results of preliminary experiments, the HE4 original solution was diluted 250-fold (1 µg/ml), 1,250-fold (0.2 µg/ml) and 3,000-fold (0.083 µg/ml), respectively, for follow-up experiments.…”

Section: Resultsmentioning

confidence: 99%

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

et al. 2014

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Abstract. Available evidence on the proliferation-promoting effect of HE4 remains controversial, and few studies have been carried out on the molecular mechanism of chemoresistance mediated by HE4. The aim of the present study was to investigate the influence of exogenous recombinant HE4 protein on proliferation and resistance to carboplatin in ovarian cancer cells. The human ovarian cancer cell line (SKOV-3) was exposed to recombinant HE4 protein (0-1 µg/ml) for different durations based on the schemes. Cell viability was evaluated by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Markers of apoptosis (Bax and Bcl-2) were assessed by western blotting. Furthermore, Affymetrix microarray analysis was performed to investigate transcriptome profiling. The differential expression of four genes was verified by quantitative real-time PCR. The HE4 protein enhanced cell viability, promoted accumulation of cells in the G2/M phase and attenuated carboplatin-induced apoptosis. HE4 markedly decreased the Bax/Bcl-2 ratio. Candidate genes (387) (236 upregulated and 151 downregulated) were obtained by microarray analysis. Among those upregulated, several Gene Ontology (GO) terms related to cell cycle regulation and proliferation were significantly overrepresented and those within the downregulated dataset included genes involved in several aspects of the DNA damage response such as positive regulation of apoptosis. No information concerning the EGFR-MAPK pathways in a recent report on HE4 was acquired. The mRNA expression of the candidate genes determined by quantitative real-time PCR was significantly correlated with the microarray data. The present study indicates that the HE4 protein plays a promotive role in the proliferation and resistance to carboplatin in ovarian cancer cells, implicating the value of HE4 to predict tumor growth potential and resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC).

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Section: Resultsmentioning

confidence: 99%

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

et al. 2014

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“…Our recent studies also showed another HRPs member, HRP-3 was highly upregulated in HCC tissues. HRP-3 can promote anchorage-dependent and -independent growth of HCC cells in vitro and xenograft tumor growth in vivo, possibly through activating the MAPK-ERK pathway [8]. In contrast to HDGF (~240aa) or HRP-3 (~212aa), HRP-2 encodes a larger protein (~671aa), and has not been characterized in previous studies.…”

Section: Introductionmentioning

confidence: 97%

HDGF-related protein-2 (HRP-2) acts as an oncogene to promote cell growth in hepatocellular carcinoma

Gao

Chen

Jin

et al. 2015

Biochemical and Biophysical Research Communications

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“…For example, HRP-3 is involved in neuritogenesis of primary cortical neurons through modulation of the neuronal cytoskeleton by interacting with tubulin [8] or heparin sulfate proteoglycans [9]. One recent study has reported an association of HRP-3 with cancer [10]. The authors of this study suggested that HRP-3 plays an essential role in the pathogenesis of HCC based on the significant upregulation of HRP-3 in human HCC tissues compared to noncancerous tissues.…”

Section: Introductionmentioning

confidence: 79%

Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

Yun

Hong

Lee

et al. 2013

Biochemical and Biophysical Research Communications

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Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer.

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HDGF-related protein-3 is required for anchorage-independent survival and chemoresistance in hepatocellular carcinomas

Abstract: These findings indicate that HRP-3 plays an essential role in HCC pathogenesis and suggest that it may serve as a novel prognostic marker and molecular target for development of drugs for treatment of HCC.

Cited by 33 publications

References 33 publications

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

HDGF-related protein-2 (HRP-2) acts as an oncogene to promote cell growth in hepatocellular carcinoma

Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

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