ArticleWorld journal of gastroenterology2014
Bortezomib effect on E2F and cyclin family members in human hepatocellular carcinoma cell lines.
Article in World journal of gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report.Bioscience reports · 2020Pooled it
- Regulation Ratio: A Singular Multi-Omic Measurement of Gene Regulatory Mechanisms.Computational and structural biotechnology journal · 2026Article
- Overexpression pattern, function, and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma.World journal of clinical oncology · 2025Article
- Article
- Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.Heliyon · 2024Review
- In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells.Pharmaceutics · 2024Article
- Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules.Pharmaceuticals (Basel, Switzerland) · 2021Review
- CDCA2 protects against oxidative stress by promoting BRCA1-NRF2 signaling in hepatocellular carcinoma.Oncogene · 2021Article
- Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Long noncoding RNA SNHG6 promotes proliferation and angiogenesis of cholangiocarcinoma cells through sponging miR-101-3p and activation of E2F8.Journal of Cancer · 2020Article
- Role of E2Fs and mitotic regulators controlled by E2Fs in the epithelial to mesenchymal transition.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Promising diagnostic and prognostic value of E2Fs in human hepatocellular carcinoma.Cancer management and research · 2019Article
- Key signaling pathways, genes and transcription factors associated with hepatocellular carcinoma.Molecular medicine reports · 2018Article
- Positioning of proteasome inhibitors in therapy of solid malignancies.Cancer chemotherapy and pharmacology · 2018Review
- miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer.Cell death & disease · 2017Article
- E2F8 is a Potential Therapeutic Target for Hepatocellular Carcinoma.Journal of Cancer · 2017Review
- Can TIE-2 expressing monocytes represent a novel marker for hepatocellular carcinoma?Hepatobiliary surgery and nutrition · 2014Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo evaluate the effects of the proteasome inhibitor bortezomib (BZB) on E2Fs and related genes in hepatocellular carcinoma (HCC) cells.
methodsThe mRNA levels of the E2F family members (pro-proliferative: E2F1-3 and anti-proliferative: E2F4-8) and of their related genes cyclins and cyclin-dependent kinases (cdks) were evaluated in two HCC cell lines following a single BZB administration. mRNA levels of the epithelial-mesenchymal transition (EMT) genes were also measured in both cell lines after BZB treatment. The BZB concentration (40 nmol/L) used was chosen to stay well below the maximal amount/cm² recommended for in vivo application, and 2 d incubation was chosen as this time point has been found optimal to detect BZB effects in our previous studies. The HCC cell lines, HepG2 and JHH6, were chosen as they display different phenotypes, hepatocyte-like for HepG2 and undifferentiated for JHH6, thus representing an in vitro model of low and high aggressive forms of HCC, respectively. The mRNA levels of the target genes were measured by two-color microarray-based gene expression analysis, performed according to Agilent Technologies protocol and using an Agilent Scan B. For the E2F family members, mRNA levels were quantified by real-time reverse transcription polymerase chain reaction (RT-PCR). Using small interfering RNA's, the effects of E2F8 depletion on cell number was also evaluated.
resultsAfter BZB treatment, microarray analysis of the undifferentiated JHH6 revealed a significant decrease in the expression of the pro-proliferative E2F member E2F2. Quantitative RT-PCR data were in keeping with the microarray analysis, and showed a significant increase and decrease in E2F8 and E2F2 mRNA levels, respectively. In contrast, BZB treatment of the hepatocyte-like HCC cell line HepG2 had a significant impact on mRNA levels of 5 of the 8 E2F members. In particular, mRNA levels of the pro-proliferative E2F members E2F1, E2F2, and of the anti-proliferative member E2F8, decreased over 80%. Notably, a reduction in E2F8 expression in HepG2 and JHH6 cells following siRNA treatment had no impact on cell proliferation. As observed with JHH6, BZB treatment of HepG2 cells induced a significant increase in mRNA levels of an anti-proliferative E2F member, E2F6 in this case. As was observed with E2F's, more dramatic changes in mRNA levels of the E2F related genes cyclins and Cdks and EMT genes were observed after BZB treatment of HepG2 compared to JHH6.
conclusionThe differential expression of E2Fs and related genes induced by BZB in diverse HCC cell phenotypes contribute to bortezomib's mechanism of action in hepatocellular carcinoma.
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