Quantitative Proteomic Signature of Liver Cancer Cells: Tissue Transglutaminase 2 Could Be a Novel Protein Candidate of Human Hepatocellular Carcinoma

2008 ◽  
Vol 7 (9) ◽  
pp. 3847-3859 ◽  
Author(s):  
Yulin Sun ◽  
Wei Mi ◽  
Jianqiang Cai ◽  
Wantao Ying ◽  
Fang Liu ◽  
...  
2011 ◽  
Vol 5 (3) ◽  
pp. 153-160 ◽  
Author(s):  
Giuseppe Carruba ◽  
Vitale Miceli ◽  
Letizia Cocciadiferro ◽  
Maurizio Zarcone ◽  
Biagio Agostara ◽  
...  

AbstractBackground:We investigated aromatase (Aro)-driven estrogen formation in non-tumoral and malignant liver tissues and cells, also in relation to expression of the estrogen receptors α and β (ERα and ERβ) and amphiregulin (AREG), aiming to gain insights into the potential role of estrogens in human hepatocellular carcinoma (HCC).Materials and methods:Chromatographic and reverse transcriptase polymerase chain reaction (RT-PCR) analyses were used to assess activity and expression of the Aro enzyme and AREG as well as the expression of wild-type and variant ERs, both in vivo and in vitro.Results:Following 24 h and 72 h incubation of liver tissues or cells with testosterone, human HCC tissues and HepG2 hepatoma cells showed elevated Aro activity (estrogen formation, respectively, of 20% and 52%–99%). By contrast, no Aro activity could be detected in non-tumoral tissues and HA22T liver cancer cells. Cirrhotic samples and Huh7 cells exhibited intermediate enzyme activity, with estrogen formation of 4% and 34%, respectively. Markedly lower or undetectable Aro mRNA levels were observed in HA22T cells and non-tumoral liver tissues compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels. Interestingly, no or low expression of wild-type ERα and ERβ could be observed in liver cancer cells and malignant tissues. However, ubiquitous expression of the hERα46 variant and occasional expression of the hERβ2/Cx variant were observed in cancer tissues and cells.Conclusions:It is noteworthy that the pattern of wild-type ERα was inversely related to Aro, whilst AREG expression was consistently associated with that of Aro. This combined evidence suggests that locally elevated Aro activity may increase malignant cell proliferation also through AREG signalling.


2010 ◽  
Vol 5 (10) ◽  
pp. 1934578X1000501 ◽  
Author(s):  
Anupam Bishayee ◽  
Erzsébet Háznagy-Radnai ◽  
Thomas Mbimba ◽  
Péter Sipos ◽  
Paolo Morazzoni ◽  
...  

Dietary antioxidants, such as anthocyanins, are helpful in the prevention and control of various diseases by counteracting the imbalance of oxidative and antioxidative factors in the living systems. Black currant (Ribes Nigrum L., Grossulariaceae) is known to contain high amounts of anthocyanins (250 mg/100 g fresh fruit). Black currant fruits have been used in Asian and European traditional medicine for the treatment of a variety of diseases. Black currant extract has recently been found to be the second most effective amongst nine different berry extracts studied for their free radical scavenging activity. Constituents present in black currant juice have been found to exert a number of health-promoting effects, including immunomodulatory, antimicrobial and antiinflammatory actions, inhibition of low-density lipoprotein, and reduction of cardiovascular diseases. Although antioxidant and antiinflammatory effects of black currant juice could be of value in preventing and treating oxidative stress- and inflammation-driven cancers, no experimental evidence is available to now. The objective of the present study was to evaluate the potential antiproliferative effects of black currant fruit skin extract against HepG2 human liver cancer cells. The aqueous extract yielded an anthocyanin-rich fraction with cyanidin-3 -O-rutinoside as one of the major anthocyanins. This fraction exhibited a potent cytotoxic effect on HepG2 cells and this effect was more pronounced than that of delphinidin and cyanidin, two major aglycones of anthocyanins present in black currant. Our results indicate, for the first time, that black currant skin containing an anthocyanin-rich fraction inhibits the proliferation of liver cancer cells, possibly due to additive as well as synergistic effects. This product could be useful in the prevention and treatment of human hepatocellular carcinoma.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lei Lv ◽  
Yujia Zhao ◽  
Qinqin Wei ◽  
Ye Zhao ◽  
Qiyi Yi

Abstract Background Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC). Methods Clinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR. Results HSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Conclusions This study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hui Du ◽  
Yun Le ◽  
Fenyong Sun ◽  
Kai Li ◽  
Yanfeng Xu

Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) is overexpressed and has an oncogenic role in hepatocellular carcinoma (HCC). Interleukin enhancer binding factor 2 (ILF2) has become research hotspot in liver cancer recently. However, it is still unclear whether and how CREB and ILF2 interact with each other. And how this interaction exerts its role in occurrence and development of liver cancer is still unclear. Here, we found that ILF2 directly bound with CREB, and this binding was essential for the malignant phenotypes of liver cancer cells. Moreover, we found that ILF2 acted as one of the upstream proteins of CREB and promoted CREB only in the protein level, whereas ILF2 expression was not regulated by CREB. Mechanistically, ILF2 bound to the pKID domain of CREB and stimulated its phosphorylation at Ser133. Taken together, our study finds a novel interaction between CREB and ILF2 in liver cancer, and this interaction might play a role in the diagnosis and remedy of liver cancer.


RSC Advances ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 1841-1845 ◽  
Author(s):  
Baiqi Wang ◽  
Hetao Chen ◽  
Rui Yang ◽  
Fang Wang ◽  
Ping Zhou ◽  
...  

The red signals from the cytoplasm of HCC cells reveal that the QD probes can specifically label liver cancer cells.


Oncotarget ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 8499-8511 ◽  
Author(s):  
Bijun Qiu ◽  
Junqi Wang ◽  
Yingxue Yu ◽  
Chao Zhen ◽  
Jinyang Gu ◽  
...  

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