Possible Down Regulation of the p16 Gene Promoter in Individuals with Hepatocellular Carcinoma

2011 ◽  
Vol 11 (9) ◽  
pp. 719-723 ◽  
Author(s):  
Oranous Bashti Shiraz ◽  
Hamid Galehdari ◽  
Majid Yavarian ◽  
Bita Geramizadeh
2011 ◽  
Vol 11 (9) ◽  
Author(s):  
Oranous Bashti Shiraz ◽  
Hamid Galehdari ◽  
Majid Yavarian ◽  
Bita Geramizadeh

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1503
Author(s):  
Oscar Wai Ho Yeung ◽  
Xiang Qi ◽  
Li Pang ◽  
Hui Liu ◽  
Kevin Tak Pan Ng ◽  
...  

Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a.


PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89976 ◽  
Author(s):  
Jie Yin ◽  
Yi-An Zhang ◽  
Tao-Tao Liu ◽  
Ji-Min Zhu ◽  
Xi-Zhong Shen

2018 ◽  
Vol 2 (11) ◽  
pp. 1408-1414 ◽  
Author(s):  
Sarah T. K. Sin ◽  
Yan Li ◽  
Ming Liu ◽  
Yun‐Fei Yuan ◽  
Stephanie Ma ◽  
...  

2021 ◽  
Author(s):  
kangming zhu ◽  
yvndi zhang ◽  
hui yvan ◽  
jing li

Abstract BackgroundLiver hepatocellular carcinoma (LIHC) is an important pathological type of liver cancer. The immune infiltration of the tumor microenvironment is negatively correlated with the overall survival rate of LIHC. At present , the role and molecular mechanism of KPNA2 in LIHC have not been elucidated, and the prognostic correlation between the two and the immune infiltration of LIHC are still unclear. Our study evaluated the role of KPNA2 in LIHC through TCGA data.MethodGene expression profiling interactive analysis (GEPIA) is used to analyze the expression of KPNA2 in LIHC. We evaluated the impact of KPNA2 on the survival of LIHC patients through the survival module. Then, We downloaded the LIHC data set from TCGA. Logistic regression was used to analyze the correlation between clinical information and KPNA2 expression. Cox regression analysis was used to analyze the clinicopathological characteristics related to the overall survival rate of TCGA patients. In addition, we used the "correlation" modules of CIBERSORT and GEPIA to explore the correlation between KPNA2 and cancer immune infiltrate. Western blotting was used to detect the expression of KPNA2.ResultUsing logistic regression for univariate analysis, increased KPNA2 expression was significantly correlated with pathological stage, tumor status, and lymph node status. In addition, multivariate analysis showed that down-regulation of KPNA2 expression, negative pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, CIBERSORT analysis was used to establish a negative correlation between the up-regulated expression of KPNA2 and the level of immune infiltration of B cells, NK cells, mast cells, and T cells. In addition, we confirmed this in the "Association" module of GEPIA. The expression of KPNA2 in LIHC tissues was significantly lower than that in adjacent normal tissues by western blotting.ConclusionThe down-regulation of KPNA2 expression is associated with a good prognosis and an increase in the proportion of immune cells in LIHC. These conclusions indicate that KPNA2 is related to the level of immune infiltration of LIHC and can be used as a potential prognostic biomarker of LIHC and a potential target for clinical tumor treatment.


2018 ◽  
Vol 115 (15) ◽  
pp. E3509-E3518 ◽  
Author(s):  
Suresh Bugide ◽  
Michael R. Green ◽  
Narendra Wajapeyee

Natural killer (NK) cell-mediated tumor cell eradication could inhibit tumor initiation and progression. However, the factors that regulate NK cell-mediated cancer cell eradication remain unclear. We determined that hepatocellular carcinoma (HCC) cells exhibit transcriptional down-regulation of NK group 2D (NKG2D) ligands and are largely resistant to NK cell-mediated eradication. Because the down-regulation of NKG2D ligands occurred at the transcriptional level, we tested 32 chemical inhibitors of epigenetic regulators for their ability to re-express NKG2D ligands and enhance HCC cell eradication by NK cells and found that Enhancer of zeste homolog 2 (EZH2) was a transcriptional repressor of NKG2D ligands. The inhibition of EZH2 by small-molecule inhibitors or genetic means enhanced HCC cell eradication by NK cells in a NKG2D ligand-dependent manner. Collectively, these results demonstrate that EZH2 inhibition enhances HCC eradication by NK cells and that EZH2 functions, in part, as an oncogene by inhibiting immune response.


2018 ◽  
Vol 22 (2) ◽  
pp. 227-236 ◽  
Author(s):  
Yingchao Wang ◽  
Wei Jing ◽  
Weijie Ma ◽  
Chunzi Liang ◽  
Hongyan Chai ◽  
...  

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