p28GANK Prevents Degradation of Oct4 and Promotes Expansion of Tumor-Initiating Cells in Hepatocarcinogenesis

Qian, You–Wen; Chen, Yao; Yang, Wen; Fu, Jing; Cao, Jie; Ren, Yibin; Zhu, Junjie; Su, Bo; Luo, Tao; Zhao, Xiaofang; Dai, Rongyang; Li, Juan–Juan; Sun, Wen; Wu, Mengchao; Feng, Gen‐Sheng; Wang, HongYang

doi:10.1053/j.gastro.2012.02.042

Cited by 60 publications

(62 citation statements)

References 31 publications

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“…In past decades, many factors involved in the progress of HCC have been identified, including TGF-β, HNF-4α, Maelstrom, LECT2, p28 and so on. [4][5][6][7][8] However, the molecular mechanisms of HCC metastasis remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[17] To gain a better understanding of the molecular characteristics of the three types of HCC, we analyzed the gene expression patterns by using cDNA microarray, which uncovered that 7.89% (668 of 8464) human genes had significantly different expression levels between SLHCC, SHCC and NHCC. [18,19] These findings, 8 together with the importance of miRNAs in regulation of genes expression, [20] led to the hypothesis that different types of HCCs may have distinct individual miRNAs expression profiles, which contribute to their characteristic clinical, pathological and molecular traits.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma

Fěng¹,

Chang²,

et al. 2015

Journal of Hepatology

158

141

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma

Fěng¹,

Chang²,

et al. 2015

Journal of Hepatology

158

141

View full text Add to dashboard Cite

“…Gankyrin is a chaperone of the ubiquitin-proteasome and a novel oncogene, and has been demonstrated to be overexpressed in numerous types of cancer (25)(26)(27), including liver cancer (28)(29)(30), breast cancer (31,32), colorectal cancer (33), estrogen-driven endometrial carcinoma (26) and oral cancer (34). Gankyrin serves an essential role in tumor occurrence and development (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). p115 is a tether protein that has an important role in a number of signaling pathways required for cell proliferation, and has been extensively studied (35,36).…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

Wang

Chen

et al. 2017

Oncology Letters

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Abstract.The transforming growth factor-β (TGF-β) signaling pathway serves a key role in the pathogenesis of liver cancer. To investigate the association between TGF-β1 and the following proteins: Proliferating cell nuclear antigen (PCNA), gankyrin, general vesicular transport factor p115 (p115), X-linked inhibitor of apoptosis protein (XIAP) and survivin, HepG2 liver cancer cells were transfected with small interfering RNA (siRNA) directed against TGF-β1, or were treated with exogenous TGF-β1. TGF-β1 protein expression levels were assessed at 72 and 96 h using western blotting, cell growth was evaluated using a Cell Counting kit-8 assay, and flow cytometry was used to examine cell cycle distribution and apoptosis. In addition, PCNA, gankyrin, p115, XIAP and survivin protein levels were evaluated using western blotting. TGF-β1 protein expression levels were decreased at 72 and 96 h following siRNA transfection, indicating that the siRNA against TGF-β1 was effective. In the TGF-β1-knockdown group, the HepG2 cells exhibited G 1 or S-phase cell cycle arrest; therefore, the number of G 2 -phase cells was decreased, cell growth was inhibited and apoptotic peaks were observed. By contrast, no significant alteration in cell cycle distribution or apoptosis was observed in the cells treated with exogenous TGF-β1. In the exogenous TGF-β1 group, PCNA and XIAP protein expression levels were increased, whereas gankyrin, p115 and survivin protein expression was observed to be dependent on the duration of treatment. By contrast, PCNA, gankyrin, XIAP and survivin protein expression decreased following TGF-β1 knockdown; however, p115 protein expression increased. In conclusion, the TGF-β1 signaling pathway may affect cell growth, cell cycle distribution and apoptosis through the regulation of PCNA, gankyrin, p115, XIAP and survivin protein expression in liver cancer. The results of the present study may improve the current understanding of the role of the TGF-β signaling pathway during the pathogenesis of liver cancer.

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“…However, the molecular mechanisms of multistep hepatocarcinogenesis remain unclear. Previous studies have shown that Gankyrin is a critical oncoprotein that is frequently overexpressed in human HCC and that is involved in the progression of HCC via the degradation of Rb and elimination of p5351314151617181920. Few reports have described the early initiating events in hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Gradually elevated expression of Gankyrin during human hepatocarcinogenesis and its clinicopathological significance

Jing

Zhang

Meng³

et al. 2014

Sci Rep

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Gankyrin is an important oncoprotein that is overexpressed in human hepatocellular carcinoma (HCC). However, the gradual alteration of Gankyrin in successive stages during human HCC development and the mechanism of Gankyrin-mediated hepatocarcinogenesis remain largely unknown. In this study, we evaluated the pattern and level of Gankyrin protein expression using immunohistochemistry in various liver tissues, including normal liver, chronic hepatitis, cirrhosis, adenomatous hyperplasia (AH), and HCC tissues, to analyze its clinicopathological significance. Furthermore, we stably transfected the shRNA-Gan vector, which targets human Gankyrin, into HepG2 cells to assess the role of Gankyrin in cell proliferation and tumorigenicity. The expression level of Gankyrin in the cytoplasm, nucleus, and whole cell was gradually elevated during consecutive stages of hepatocarcinogenesis. The nuclear Gankyrin level in AH was significantly higher than that in normal liver, chronic hepatitis, and cirrhotic tissues. The cytoplasmic, nuclear, and total cellular Gankyrin expression levels in HCC were significantly correlated with capsular invasion and intrahepatic metastasis. Silencing Gankyrin expression using shRNA-Gan repressed tumor cell proliferation, tumorigenicity, migration, and invasion in vitro. Our findings demonstrate that Gankyrin is aberrantly expressed beginning at the initiation stage and plays an important role in the initiation, promotion, and progression of hepatocarcinogenesis.

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p28GANK Prevents Degradation of Oct4 and Promotes Expansion of Tumor-Initiating Cells in Hepatocarcinogenesis

Cited by 60 publications

References 31 publications

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

Gradually elevated expression of Gankyrin during human hepatocarcinogenesis and its clinicopathological significance

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