scholarly journals Cancer chemoprevention by an adenosine derivative in a model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769119 ◽  
Author(s):  
Gabriela Velasco-Loyden ◽  
Lidia Pérez-Martínez ◽  
Susana Vidrio-Gómez ◽  
Julio Isael Pérez-Carreón ◽  
Victoria Chagoya de Sánchez
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cancer Chemoprevention ◽  
Cell Cycle Inhibitor ◽  
Collagen Expression ◽  
Induce Hepatocarcinogenesis ◽  
Glutamyl Transferase ◽  
Hepatocyte Growth ◽  
Therapeutic Compound

Hepatocellular carcinoma is one of the most common cancers, and approximately 80% develop from cirrhotic livers. We have previously shown that the aspartate salt of adenosine prevents and reverses carbon tetrachloride–induced liver fibrosis in rats. Considering the hepatoprotective role of this adenosine derivative in fibrogenesis, we were interested in evaluating its effect in a hepatocarcinogenesis model induced by diethylnitrosamine in rats, where multinodular cancer is preceded by cirrhosis. Rats were injected with diethylnitrosamine for 12 weeks to induce cirrhosis and for 16 weeks to induce hepatocarcinogenesis. Groups of rats were treated with aspartate salt of adenosine from the beginning of carcinogen administration for 12 or 18 weeks total, and another group received the compound from weeks 12 to 18. Fibrogenesis was estimated and the proportion of preneoplastic nodules and tumors was measured. The apoptotic and proliferation rates in liver tissues were evaluated, as well as the expression of cell signaling and cell cycle proteins participating in hepatocarcinogenesis. The adenosine derivative treatment reduced diethylnitrosamine-induced collagen expression and decreased the proportion of nodules positive for the tumor marker γ-glutamyl transferase. This compound down-regulated the expression of thymidylate synthase and hepatocyte growth factor, and augmented the protein level of the cell cycle inhibitor p27; these effects could be part of its chemopreventive mechanism. These findings suggest a hepatoprotective role of aspartate salt of adenosine that could be used as a therapeutic compound in the prevention of liver tumorigenesis as described earlier for hepatic fibrosis.

scholarly journals Melatonin enhances the anti-tumor effect of sorafenib via AKT/p27-mediated cell cycle arrest in hepatocarcinoma cell lines

RSC Advances ◽  
2017 ◽  
Vol 7 (34) ◽  
pp. 21342-21351 ◽  
Author(s):  
Fei Long ◽  
Chengyong Dong ◽  
Keqiu Jiang ◽  
Yakun Xu ◽  
Xinming Chi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cycle Arrest ◽  
Hepatocarcinoma Cell ◽  
Proposed Model ◽  
Hcc Cells

Proposed model elucidating the role of MT in regulating the proliferation of hepatocellular carcinoma (HCC) cells treated with sorafenib.

c-Abl-mediated tyrosine phosphorylation of JunB is required for Adriamycin-induced expression of p21

2015 ◽  
Vol 471 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Noritaka Yamaguchi ◽  
Ryuzaburo Yuki ◽  
Sho Kubota ◽  
Kazumasa Aoyama ◽  
Takahisa Kuga ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Tyrosine Phosphorylation ◽  
Dna Damage Response ◽  
Induced Expression ◽  
Cell Cycle Inhibitor ◽  
Damage Response

We analysed the role of c-Abl-mediated tyrosine phosphorylation of JunB in Adriamycin-induced DNA damage response. Tyrosine phosphorylation of JunB was found to be required for expression of the cell cycle inhibitor p21 upon Adriamycin stimulation.

scholarly journals Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5787 ◽  
Author(s):  
Jun Shi ◽  
Guangqiang Ye ◽  
Guoliang Zhao ◽  
Xuedong Wang ◽  
Chunhui Ye ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Target Genes ◽  
Expression Profiles ◽  
M Phase ◽  
Non Coding Rnas ◽  
Regulatory Model ◽  
Microarray Analyses ◽  
The Relationship

Objective To investigate the interaction of non-coding RNAs (ncRNAs) in hepatocellular carcinoma. Methods We compared the ncRNAs and mRNAs expression profiles of hepatocellular carcinoma and adjacent tissue by microarray and RT-PCR. The relationship between different ncRNAs and mRNA was analyzed using bioinformatics tools. A regulatory model of ncRNAs in hepatocellular carcinoma cells was developed. Results A total of 1,704 differentially expressed lncRNAs, 57 miRNAs, and 2,093 mRNAs were identified by microarray analyses. There is a co-expression relationship between two ncRNAs (miRNA-125b-2-3p and lncRNA P26302). Bioinformatics analysis demonstrated cyclin-dependent kinases 1 and CyclinA2 as potential targets of miR-125b-2-3p and Polo-like kinase 1 as potential target of lncRNAP26302. All three gene are important components in the G2/M phase of cell cycle. Subsequently real-time polymerase chain reaction (PCR) studies confirmed these microarray results. Conclusion MiR-125b-2-3p and lncRNAP26302 may affect the G2/M phase of the cell cycle through the regulation of their respective target genes. This study shows a role of ncRNAs in pathogenesis of hepatocellular carcinoma at molecular level, providing a basis for the future investigation aiming at early diagnosis and novel treatment of hepatocellular carcinoma.

scholarly journals Microarray Data Mining and Preliminary Bioinformatics Analysis of Hepatitis D Virus-Associated Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Zhe Yu ◽  
Xuemei Ma ◽  
Wei Zhang ◽  
Xiujuan Chang ◽  
Linjing An ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
The Cancer Genome Atlas ◽  
Venn Diagram ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hepatitis D ◽  
Increased Risk ◽  
Key Genes

Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, CDCA5, CENPH, and MCM7, and 4 novel genes, namely, CDC6, CDC45, CDCA8, and MCM4, which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The CDCA8 and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis.

scholarly journals Predictors of Recurrence of Hepatocellular Carcinoma after Transarterial Chemoembolization: Role of Hepatocyte Growth Factor

2020 ◽  
Vol 10 (06) ◽  
pp. 151-165
Author(s):  
Amr Mohamed Zaghloul ◽  
Ahmed Sedky ◽  
Ali Hussein Mohammed ◽  
Samer A. El-Sawy ◽  
Ahmed Abd El Rady Ahmed ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Transarterial Chemoembolization ◽  
Predictors Of Recurrence ◽  
Hepatocyte Growth

scholarly journals The role of Pim-2 in apoptotic signal transduction pathway of hepatocellular carcinoma

2017 ◽  
Vol 4 (4) ◽  
pp. 1380 ◽  
Author(s):  
Jiahai Chen ◽  
Xiaoli Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Signal Transduction ◽  
Mrna Expression ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Qrt Pcr

Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. The objective was to investigate the role of serine/threonine kinase Pim-2 in apoptosis signal transduction pathway, because there is little study about its contribution to apoptosis in hepatocellular carcinoma.Methods: The Pim-2 gene and protein expression were examined by qRT-PCR, Western blot and immunohistochemical stain in HCC tissues and normal liver tissues. The plasmid pCI-neo-Pim2 was transfected into human hepatoma cell line SMMC7721 by lipofectamine. Total RNAs were extracted from SMMC7721 cell in logarithm growth phase. The mRNA expression of Pim-2, Akt-1 (protein kinase B), 4E-BP1 (translation repressor of mammalian target of rapamycln), SOCS-1 (repressor of cytokine), Bad（Bcl-xL/Bcl-2 associated death promoter, Bim（Bc1-2 interacting mediator of cell death）and Puma (p53 upregulated modulator of apoptosis) were identified by qRT-PCR. The cell cycle of post-transfected SMMC7721 cells was assessed by flow cytometry.Results: Pim-2 expression was enhanced in HCC. In post-transfected SMMC7721 cells, Pim-2 mRNA expression was up-regulated, level of Bad mRNA was attenuated, furthermore, the transcription level of Akt-1, SOCS-1, 4E-BP1, Bim and Puma gene wasn’t variety. Up-graulated Pim-2 can’t cause distinct change of cell cycle or apoptosis in hepatoma cell.Conclusions: The serine/threonine kinase Pim-2 plays an import role in the development of HCC, Pim-2 dependent maintenance of cell size and survival correlated with its ability to maintain down-regulated expression of the BH3 protein Bad. Pim-2 is not a trigger in cell-autonomous survival or inhibiting apoptosis in hepatocellular carcinoma. Pim-2 is a redundancy pathway of survival signaling.

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