Combining targeted therapies with HDAC inhibitors to tackle the p53 signaling pathway in hepatocellular carcinoma

2021 ◽  
Author(s):  
L Brandes ◽  
E Aschenbrenner ◽  
K Pollinger ◽  
K Gülow ◽  
C Kunst ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Targeted Therapies ◽  
Hdac Inhibitors ◽  
P53 Signaling ◽  
P53 Signaling Pathway

scholarly journals Paired box gene 5is a novel tumor suppressor in hepatocellular carcinoma through interaction with p53 signaling pathway

Hepatology ◽  
2011 ◽  
Vol 53 (3) ◽  
pp. 843-853 ◽  
Author(s):  
Weili Liu ◽  
Xiaoxing Li ◽  
Eagle S.H. Chu ◽  
Minnie Y.Y. Go ◽  
Lixia Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Signaling Pathway ◽  
P53 Signaling ◽  
P53 Signaling Pathway

scholarly journals Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Shui Liu ◽  
Xiaoxiao Yao ◽  
Dan Zhang ◽  
Jiyao Sheng ◽  
Xin Wen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Gene Network ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Mrna Levels ◽  
Qrt Pcr ◽  
P53 Signaling ◽  
Tf Gene ◽  
P53 Signaling Pathway

Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC. We found that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. In addition, we confirmed that the mRNA levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR validation. Therefore, we speculated that miR-181a-5p, which was upregulated in HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression of HCC by p53 signaling pathway. Overall, the study provides support for the possible mechanisms of progression in HCC.

scholarly journals Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Ying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Replication ◽  
Signaling Pathway ◽  
Excision Repair ◽  
Tca Cycle ◽  
Hazard Ratio ◽  
Pyrimidine Metabolism ◽  
Citrate Cycle ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma remains unknown. The aim of our study was to investigate the role and clinical significance of E2F2 in hepatocellular carcinoma (HCC).Methods: HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression was applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier was employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene set enrichment analysis (GSEA).Results: The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), clinical stage (OR =1.74 for III-IV vs. I-II, p=0.03), T (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma alpha fetoprotein (AFP) value (OR =3.18 for AFP≥400 vs AFP＜20, p= 2.16E-04; OR=2.50 for 20≤AFP＜400 vs AFP＜20, p=2.56E-03). Increased E2F2 had an unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p =0.004 , hazard ratio [HR]= 2.4 (95% CI [1.3-4.2])), DFI (P =0.029, hazard ratio [HR] = 2.0 (95% CI [1.1-3.7])) and PFI (P =0.005, hazard ratio [HR] = 2.2 (95% CI [1.3-3.9])) . GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.Conclusions: Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participate in the initial and progression of HCC.

scholarly journals Small nucleolar RNA 42 promotes the growth of hepatocellular carcinoma through the p53 signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ganggang Wang ◽  
Jinghua Li ◽  
Ye Yao ◽  
Yingyi Liu ◽  
Peng Xia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Prognostic Biomarker ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
P53 Signaling ◽  
P53 Signaling Pathway

AbstractRecent studies show that small nucleolar RNAs (snoRNAs) play an important role in tumorigenesis. SNORA42 is a potential therapeutic target and prognostic biomarker for various cancers, and the aim of the present study was to investigate the function and clinical relevance of SNORA42 in hepatocellular carcinoma (HCC). We detected the expression levels of SNORA42 in HCC and normal liver tissue samples, as well as in tumor and hepatocyte-derived cell lines. SNORA42 was significantly upregulated in the HCC tissues and cells compared to the adjacent liver tissues and normal hepatocytes. Furthermore, overexpression of SNORA42 correlated with poor prognosis in the HCC patients. Knocking down SNORA42 in HCC cell lines decreased their proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo. In contrast, ectopic expression of SNORA42 promoted HCC cell proliferation and inhibited apoptosis. Mechanistically, SNORA42 exerted its oncogenic effects by targeting the p53 signaling pathway and cell cycle transition. In conclusion, SNORA42 acted as an oncogene in HCC and was a potential prognostic biomarker and therapeutic target.

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