The importance of ubiquitin E3 ligases, SCF and APC/C, in human cancers

Bochis, Ovidiu Vasile; Fetică, Bogdan; Vlad, Cătălin; Achimaș-Cădariu, Patriciu; Irimie, Alexandru

doi:10.15386/cjmed-377

Cited by 12 publications

(12 citation statements)

References 56 publications

(140 reference statements)

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“…The basis of these capabilities is genetic instability and chronic inflammation (14). The E2F family is downstream of CDK-Rb-E2Fs in a cell cycle regulation network (15), and is a crutial transcriptional regulatory factor in the cell cycle. It has been reported that they not only play an important role in cell proliferation and maintain gene stability (13), but also have critical effects on apoptosis, metabolism, differentiation, DNA damage and repair, angiogenesis and so on (16,17).…”

Section: Discussionmentioning

confidence: 99%

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

Zeng

Cao

Tang³

2020

Preprint

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Background E2F 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 TCGA. Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression was applied to analyze the the relationship between the expression of E2F2 and clinicalpathologic charateristics. Cox regression and Kaplan-Meier was employed to evaluate the correlation between clinicopathologic features and survial. 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 prominentlly correlated with tumor grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), tumor stage (OR =1.74 for III-IV vs. I-II, p=0.03), topography (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 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 a 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 = 4.4E-04, HR = 2.4 (95% CI [1.5-3.8])) and DSS (p = 7.6E-04, HR = 3.0, (95% CI [1.6-5.6])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signalling 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 promissing independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signalling 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.

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Section: Discussionmentioning

confidence: 99%

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

Zeng

Cao

Tang³

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The basis of these capabilities is genetic instability and chronic in ammation [18]. The E2F family is downstream of CDK-E2Fs-Rbnetwork in a cell cycle regulation network [19,20], and is a crucial transcriptional regulatory factor in the cell cycle. It has been reported that they not only play an important role in cell proliferation and maintain gene stability [17], but also have critical effects on apoptosis, metabolism, differentiation, DNA damage and repair, angiogenesis and so on [21,22].…”

Section: Discussionmentioning

confidence: 99%

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

Zeng

Cao

Tang³

2020

Preprint

View full text Add to dashboard Cite

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.

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“…Нарушение процессов убиквитинзависимого протеолиза и деградации лизина наблюдается при многих злокачественных заболеваниях. В частности, посредством убиквитинпротеосомной системы осуществляется регуляция на уровне белков модуляторов клеточного цикла -циклинзависимых киназ и p53 [11]. В целом стоит отметить, что сигнальные механизмы, изменения которых выявлены посредством биоинформационного анализа в меланоме, известны как играющие роль в меланомогенезе, что в свою очередь свидетельствует об адекватности исследования, проводимого на основе микрочипирования.…”

Section: Discussionunclassified