scholarly journals Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and hepatocellular carcinoma.

2006 ◽  
Vol 53 (1) ◽  
pp. 237-241 ◽  
Author(s):  
Hanna Czeczot ◽  
Dorota Scibior ◽  
Michał Skrzycki ◽  
Małgorzata Podsiad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tissue ◽  
Normal Liver ◽  
Cancer Tissue ◽  
Glutathione Level ◽  
Normal Tissues ◽  
Control Tissue ◽  
Cirrhotic Tissue ◽  
Cancer Tissues ◽  
Gst Activity

We investigated glutathione level, activities of selenium independent GSH peroxidase, selenium dependent GSH peroxidase, GSH S-transferase, GSH reductase and the rate of lipid peroxidation expressed as the level of malondialdehyde in liver tissues obtained from patients diagnosed with cirrhosis or hepatocellular carcinoma. GSH level was found to be lower in malignant tissues compared to adjacent normal tissues and it was higher in cancer than in cirrhotic tissue. Non-Se-GSH-Px activity was lower in cancer tissue compared with adjacent normal liver or cirrhotic tissue, while Se-GSH-Px activity in cancer was found to be similar to its activity in cirrhotic tissue and lower compared to control tissue. An increase in GST activity was observed in cirrhotic tissue compared with cancer tissue, whereas the GST activity in cancer was lower than in adjacent normal tissue. The activity of GSH-R was similar in cirrhotic and cancer tissues, but higher in cancer tissue compared to control liver tissue. An increased level of MDA was found in cancer tissue in comparison with control tissue, besides its level was higher in cancer tissue than in cirrhotic tissue. Our results show that the antioxidant system of cirrhosis and hepatocellular carcinoma is severely impaired. This is associated with changes of glutathione level and activities of GSH-dependent enzymes in liver tissue. GSH and enzymes cooperating with it are important factors in the process of liver diseases development.

scholarly journals Overexpression of NNT-AS1 Activates TGF-β Signaling to Decrease Tumor CD4 Lymphocyte Infiltration in Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yakun Wang ◽  
Lei Yang ◽  
Xichen Dong ◽  
Xin Yang ◽  
Xinxue Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Tissue ◽  
Tumor Immune Evasion ◽  
Normal Tissues ◽  
Mechanistic Investigation ◽  
Cd4 Lymphocyte ◽  
Cancer Tissues

Nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) is a long noncoding RNA (lncRNA) that has been shown to be overexpressed in hepatocellular carcinoma (HCC). However, the molecular mechanism involving NNT-AS1 in HCC remains to be extensively investigated. The activation of TGF-β signaling inhibits tumor-infiltrating lymphocytes (TILs) and results in tumor immune evasion. We thus planned to explore the mechanism by which NNT-AS1 activates the TGF-β signaling pathway and inhibits TILs in HCC. High levels of NNT-AS1 were detected in HCC tissues by both RNAscope and real-time quantitative PCR (RT-qPCR) assays. The levels of proteins involved in TGF-β signaling and those of CD4 T lymphocytes were quantified by immunohistochemistry (IHC). HCC cell lines (HepG2 and Huh7) were used to explore the effects of NNT-AS1 on TGF-β signaling activation. In these analyses, RNAscope detection demonstrated that NNT-AS1 levels were significantly increased in HCC cancer tissues ( P = 0.0001 ). In addition, the elevated NNT-AS1 levels in cancer tissue were further confirmed by RT-qPCR analysis of HCC cancer tissues ( n = 64 ) and normal tissues ( n = 26 ) ( P = 0.0003 ). Importantly, the overall survival time of HCC patients who exhibited higher levels of NNT-AS1 expression was significantly shorter than that of HCC patients who had lower levels of NNT-AS1 expression ( P = 0.0402 ). Further mechanistic investigation indicated that NNT-AS1 inhibition significantly decreased the levels of TGF-β, TGFBR1, and SMAD5 in HCC cells. In HCC tissues, IHC detection showed that relatively high NNT-AS1 levels were associated with a reduction in infiltrated CD4 lymphocyte numbers. In conclusion, this research identifies a novel mechanism by which NNT-AS1 impairs CD4 T cell infiltration via activation of the TGF-β signaling pathway in HCC.

Aberrant β-catenin activity in hepatoid adenocarcinoma of the stomach

2020 ◽  
Vol 20 ◽  
Author(s):  
Nan Wang ◽  
Rui Kong ◽  
Wei Han ◽  
Jie Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pearson Correlation ◽  
Clinicopathological Characteristics ◽  
Cancer Tissue ◽  
Hepatoid Adenocarcinoma ◽  
Tumor Initiating Cells ◽  
Significant Difference ◽  
Diagnostic Confusion ◽  
Hematoxylin And Eosin ◽  
Cancer Tissues

Background: Hepatoid adenocarcinoma of the stomach (HAS) has been recognized as a rare primary gastric tumor characterized by hepatocellular carcinoma-like histology. HAS often causes diagnostic confusion with conventional gastric adenocarcinoma (CGA) due to the difficulty to detect hepatoid differentiation solely based on findings from hematoxylin and eosin (H&E) staining. Hence, HAS should be distinguished from solid-type CGA based on their different biological behaviors. β-catenin is highly expressed in hepatocellular carcinoma (HCC), which is involved in the maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. Methods and Results: Given the dearth of HAS cases, systematic examination of the expression of β-catenin in HAS remains under-explored. In this study, 14 cases were subjected to immunostaining with with AFP, β-catenin, glypican3, hepar-1 and CerbB-2. In parallel, the clinicopathological characteristics of these patients were collected. We detected statistically significant difference in the expression of β-catenin (P = 0.000), glypican3 (P = 0.019), and hepar-1 (P = 0.007) between HAS cancer tissues and the adjacent non-cancerous tissues. Furthermore, a significant correlation was observed between the expression of β-catenin in HAS cancer tissue and adjacent tissue (Pearson correlation coefficient: 0.686, P = 0.007). Moreover, in cancer tissues, a significant correlation was observed between the expression of β-catenin and survival time (Spearman correlationcoefficient= - 0.482, P = 0.003). However, we found the expression of β-catenin did not correlate with the degree of tumor differentiation and tumor size, age, gender, serum AFP levels, microinvasion, and metastasis (P > 0.05). Conclusion: Our findings establish β-catenin as a useful marker that can distinguish HAS from CGA and may improve the early diagnosis to guide the appropriate and timely treatment of HAS patients.

scholarly journals Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Jie Zhang ◽  
Qianqian Song ◽  
Jinxia Liu ◽  
Lina Lu ◽  
Yuqing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Regulatory Subunit ◽  
Mrna Levels ◽  
Cyclin Dependent Kinase ◽  
Normal Tissues ◽  
Hcc Cells

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a member of the cell cycle-dependent protein kinase subunit family, which is implicated as an oncogene in various malignancies. However, the clinical significance, oncogenic functions, and related mechanisms of CKS2 in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, expression features and prognostic value of CKS2 were evaluated in the bioinformatic databases and HCC tissues. The effects of CKS2 on the malignant phenotypes of HCC cells were explored in vitro. According to the analyses of three bioinformatic databases, mRNA levels of CKS2 were elevated in HCC tissues compared with the normal tissues. Immunohistochemical assays found that high CKS2 expression was closely associated with liver cirrhosis (P=0.019), poor differentiation (P=0.02), portal vein invasion (P<0.001), TNM stage (P=0.019), tumor metastasis (P=0.008), and recurrence (P=0.003). The multivariate regression analyses suggested that CKS2 was an independent prognostic factor for overall survival (HR=2.088, P=0.014) and disease-free survival (HR=2.511, P=0.002) of HCC patients. Moreover, the bioinformatic analyses indicated that CKS2 might be associated with the malignant phenotypes in HCC progression. In addition, in vitro assays showed that CKS2 expression was higher in HCC cell lines than in normal liver cells. Knockdown of CKS2 remarkably repressed the proliferation, colony formation (P=0.0003), chemoresistance, migration (P=0.0047), and invasion (P=0.0012) of HCC cells. Taken together, overexpression of CKS2 was significantly correlated with poor prognosis of HCC patients and the malignant phenotypes of HCC cells, suggesting that it was a novel prognostic biomarker and potential target of HCC.

scholarly journals Long non-coding RNA LINC00641 promotes the growth and invasiveness of hepatocellular carcinoma by antagonizing miR-501-3p

2021 ◽  
Author(s):  
Haitao Xie ◽  
Hui Zhou ◽  
Yan Jiang ◽  
Wenqian Xu ◽  
Leping Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Proliferation And Invasion ◽  
Hcc Cells

IntroductionLong non-coding RNA LINC00641 has been reported to regulate tumor progression in several cancers. However, the expression and function of LINC00641 in hepatocellular carcinoma (HCC) is still unclear.Material and methodsIn this study, we measured the expression of LINC00641 in 79 pairs of HCC and adjacent normal liver tissues. The clinical significance of LINC00641 in HCC was explored. We also investigated the function of LINC00641 in HCC proliferation and invasion.ResultsWe observed that LINC00641 expression was significantly increased in HCC relative to normal tissues (P < 0.0001). High expression of LINC00641 was significantly associated with vascular invasion, advanced TNM stage, and reduced overall survival in HCC patients. Knockdown of LINC00641 inhibited the proliferation, colony formation, and invasion of HCC cells. In contrast, overexpression of LINC00641 promoted HCC cell growth and invasiveness. In vivo studies confirmed that knockdown of LINC00641 restrained tumorigenesis of HCC cells. Mechanistic studies revealed that LINC00641 inhibited the expression of miR-501-3p, which has been previously reported to act as a tumor suppressor in HCC. Furthermore, luciferase reporter assays validated that LINC00641 harbored a target site for miR-501-3p. Rescue experiments demonstrated that LINC00641-induced proliferation and invasion of HCC cells was reversed by co-expression of miR-501-3p.ConclusionsTaken together, LINC00641 contributes to aggressive phenotype of HCC cells by sponging miR-501-3p and represents a promising therapeutic target for this disease.

scholarly journals miR-183-5p promotes proliferation and migration in hepatocellular carcinoma by targeting IRS1 and its association with patient survival

2020 ◽  
Vol 35 (3) ◽  
pp. 83-89
Author(s):  
Rong Yan ◽  
Kang Li ◽  
Dawei Yuan ◽  
Haonan Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Progression ◽  
Normal Tissues ◽  
Report Analysis ◽  
In Vitro Effects ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Background: MiR-183-5p plays an important role in the pathophysiology of many tumors, while the role of MiR-183-5p in liver cancer is unclear. Methods: In this study, quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect the expression of miR-183-5p in liver cancer cell lines, liver cancer tissues, and normal tissues adjacent to the cancer, and to explore the mechanism of miR-183-5p regulating liver cancer progression. The in vitro effects of miR-183-5p were evaluated by CCK-8, colony formation test, and wound healing test. Various databases were used to predict the target mRNA of miR-183-5p and verified by luciferase report analysis. In addition, the effects of miR-183-5p and its target gene on the survival of patients with liver cancer were also analyzed. Results: miR-183-5p was highly expressed in hepatocellular carcinoma cells and tissues, and was related to some clinicopathological features. MiR-183-5p can promote the proliferation and migration of liver cancer cells. Using the bioinformatics database, we proved that miR-183-5p is related to the survival of liver cancer patients. Insulin receptor substrate 1 (IRS1) is a target of miR-183-5p, and luciferase analysis confirmed that miR-183-5p combines with the 3′-untranslated region (3′-UTR) of IRS1. Conclusion: The miR-183-5p/IRS1 axis may be a new target for liver cancer research.

scholarly journals The expression and Clinical Significance of miRNA-135a and Bach1 in colorectal cancer

2021 ◽  
Author(s):  
Yang zhi Jiang ◽  
Qing Guo Tao ◽  
fei yan Zhu
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Clinical Information ◽  
Control Group ◽  
Tumor Control ◽  
Cancer Tissue ◽  
Expression Levels ◽  
Real Time Quantitative Pcr ◽  
Normal Tissues ◽  
Cancer Tissues

BACKGROUND AIM To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information.  Methods   60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinomas and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represented mean±SD of three independent experiments. P&lt;0.05 was considered statistically significant. Results  miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P&lt;0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P&lt;0.01). Bach1 and miRNA-135a were negatively correlated.  Conclusions:  The levels of miRNA-135a and Bach1 were opposite, the over-expression of miRNA-135a might downregulated the expression of Bach1, which might be involved in the pathogenesis of colorectal cancer.

scholarly journals Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Junjie Jiang ◽  
Hui-Ju Wang ◽  
Xiao-Zhou Mou ◽  
Huanqing Zhang ◽  
YiZhen Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Clinicopathological Parameters ◽  
Expression Array ◽  
Chi Square ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
The Relationship ◽  
Liver Tissues

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC. Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly. Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues. Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.

scholarly journals Telocytes Promote the Metastasis of Hepatocellular Carcinoma by Activating ERK Signaling Pathway and Sponging miR-942-3p to Impact MMP9

2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Cancer Tissue ◽  
Proliferative Potential ◽  
Cancer Tissues ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma(HCC) in China is considered as a familiar malignant tumor with poor prognosis, high metastasis and disease relapse. Telocytes(TCs) have been verified to participate in progresses of tumorigenesis, invasions and migrations by secreting functional proteins and transmitting cell-to-cell information. Extracellular signal-regulared protein kinase(ERK) signal pathway is a vital mechanism driving cell proliferation, metastasis and apoptosis, but whether this molecular signaling mechanism contributes to matrix metalloproteinase-9(MMP) expression of TCs remains unclear. Methods: Telocytes and MMP9 expression in the liver cancer tissues are measured by immunohistochemistry assay, Westen blot assay and RT-PCR technique, meanwhile primary telocytes from liver para-cancer tissues are cultured in vitro. To demonstrate the function of telocytes for hepatocellular carcinoma, the metastatic cancer animal model is established by three typs of liver cancer cell-lines in vivo. Results: In our study, we elucidate that TCs in the para-cancer tissue can promote the metastasis of HCC cells by MMP-9 expression, in vitro and in vivo. PDGF derived from HCC cells has a capacity to activate Ras/ERK signaling pathway of TC as a result of accelerating MMP-9 expression, but it’s no significant for proliferative potential and apoptotic rate of TCs. While tyrosine kinase inhibitors and miR-942-3p suppress MMP-9 expression to make loss functions of TCs. Various mutations of TCs are also tested and single nucleotide polymorphisms of MMP-9 may be the potentially molecular mechanism of increasing protein expression in the invasive process of HCC. Conclusion: Our results demonstrate two potential mechanisms between HCC cells and TCs, suggesting that TC is a novel marker and target on deciphering reasons of cancer metastasis.

scholarly journals Gene Expression Characteristics of Liver Tissue Reveal the Underlying Pathogenesis of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Congfang Guo ◽  
Xiang Guo ◽  
Yudong Rong ◽  
Yirui Guo ◽  
Li Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signal Transduction ◽  
Liver Cancer ◽  
Liver Tissue ◽  
Primary Liver Cancer ◽  
Cancer Tissue ◽  
Hypergeometric Test ◽  
Functional Interpretation ◽  
Healthy Liver ◽  
Differential Genes

Background. Hepatocellular carcinoma (HCC) is high-mortality primary liver cancer and the most common malignant tumor in the world. This study is based on a hepatocellular carcinoma-related dysfunction module designed to explore the dysregulation of genes in liver cancer tissue. Methods. By downloading the relevant data on the GEO database, we performed a differential analysis of healthy liver tissue and liver cancer tissues as well as healthy liver tissue and hepatocellular carcinoma tissue and then obtained two sets of differential genes and combined them. We performed a cointerpretation analysis of these differential genes and constructed related functional disorder modules. A hypergeometric test was performed to calculate the potential regulatory effects of multiple factors on the module, and a series of ncRNA and TF regulators were identified. We obtained a total of 4479 differentially expressed genes in hepatocellular carcinoma, and these genes were clustered into ten hepatocellular carcinoma-related functional interpretation disorder modules. Results. Enrichment analysis revealed that these modular genes are mainly involved in signal transduction including cell cycle, TGF-beta signal transduction, and p53 signal transduction. Depending on the predictive analysis of multidimensional regulators, 323 ncRNAs and 52 TF-mediated hepatocellular carcinoma-related dysregulation modules were found to regulate disease progression. Conclusions. Based on a series of investigations, it was found that miR-30b-5p may participate in the peroxisome signal transduction by downregulating ABCD3-mediated module 1, thereby promoting the development and progression of hepatocellular carcinoma. Our research results not only provide a theoretical basis for biologists to study hepatocellular carcinoma further but also offer new methods and new ideas for the personalized care and treatment of hepatocellular carcinoma.

scholarly journals Circular RNA circRHOBTB3 is downregulated in hepatocellular carcinoma and suppresses cell proliferation by inhibiting miR-18a maturation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Gang Hu ◽  
Shusen Zhai ◽  
Sheng Yu ◽  
Zhen Huang ◽  
Ran Gao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Expression Vector ◽  
Circular Rna ◽  
Precursor Cell ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
Suppress Cell Proliferation ◽  
Hcc Cells

Abstract Background Circular RNA circRHOBTB3 has been characterized as a tumor suppressor in gastric cancer, while its role in hepatocellular carcinoma (HCC) is unknown. This study was carried out to analyze the role of circRHOBTB3 in HCC. Methods In this study, circRHOBTB3, mature miR-18a, and miR-18a precursor in HCC and paired non-cancer tissues were detected by RT-qPCR. The role of circRHOBTB3 in the production of mature miR-18a was explored by transfecting circRHOBTB3 expression vector into HCC cells, followed by RT-qPCR to determine the expression of mature miR-18a and miR-18a precursor. The role of circRHOBTB3 and miR-18a in HCC cell proliferation was studied using CCK-8 assay. Results CircRHOBTB3 was under-expressed in HCC compared to normal tissues. In HCC cells, circRHOBTB3 overexpression decreased mature miR-18a level but not miR-18a precursor. Cell proliferation analysis showed that circRHOBTB3 overexpression decreased cell proliferation while miR-18a overexpression increased cell proliferation. Moreover, circRHOBTB3 suppressed the role of miR-18a in cell proliferation. Conclusions CircRHOBTB3 is downregulated in HCC and may suppress cell proliferation by reducing miR-18a production.

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