Effects of E2F1–cyclin E1–E2 circuit down regulation in hepatocellular carcinoma cells

Farra, Rossella; Dapas, Barbara; Pozzato, Gabriele; Scaggiante, Bruna; Agostini, Francesco; Zennaro, Cristina; Grassi, Mario; Rosso, Natalia; Giansante, Carlo; Fiotti, Nicola; Grassi, Gabriele

doi:10.1016/j.dld.2011.07.007

Cited by 42 publications

(48 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among many other cell cycle genes, E2f1 plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage (e.g. hepatic metabolites of AFB1 are genotoxic) and oncogene activation [34], [35]. We queried the RNA-Seq dataset (containing all possible AFB1-induced gene changes by DESeq) for hub genes which we defined as controlling ≥5 downstream genes that could be directly or indirectly regulated by E2f1 using IPA’s Grow Pathway algorithm (Table S10).…”

Section: Resultsmentioning

confidence: 99%

RNA-Seq Profiling Reveals Novel Hepatic Gene Expression Pattern in Aflatoxin B1 Treated Rats

Merrick

Phadke²,

Auerbach

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1’s carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT’s) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the rat transcriptome contains many previously unidentified, AFB1-responsive exons and transcripts supporting RNA-Seq’s capabilities to provide new insights into AFB1-mediated gene expression leading to hepatocellular carcinoma.

show abstract

Section: Resultsmentioning

confidence: 99%

RNA-Seq Profiling Reveals Novel Hepatic Gene Expression Pattern in Aflatoxin B1 Treated Rats

Merrick

Phadke²,

Auerbach

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The human lymphocytes from healthy donors, the human T‐lymphoblastic CCRF‐CEM and the human hepatocarcinoma HepG2 lines were cultured as described . The chronic myelogenous leukaemia K562, histiocytic lymphoma U937, Burkitt's lymphoma Raji; T‐cell leukaemia Jurkat cell lines were cultured in 10% serum containing RPMI 1640 medium .…”

Section: Methodsmentioning

confidence: 99%

The more basic isoform of eEF1A relates to tumour cell phenotype and is modulated by hyper‐proliferative/differentiating stimuli in normal lymphocytes and CCRF‐CEM T‐lymphoblasts

Scaggiante

Dapas

Pozzato

et al. 2012

Hematological Oncology

Self Cite

View full text Add to dashboard Cite

The elongation factor 1A proteins (eEF1A1/A2) are known to play a role in tumours. We previously found that a more basic isoform of eEF1A (MBI-eEF1A) is present in the cytoskeletal/nuclear-enriched extracts of CCRF-CEM T-lymphoblasts but not in those of normal lymphocytes. To obtain deeper knowledge about MBI-eEF1A biology, we investigate from which of the eEF1A proteins, eEF1A1 or eEF1A2, MBI-eEF1A originates and the possibility that its appearance can be modulated by the differentiated or proliferative cell status. CCRF-CEM T-lymphoblasts and normal lymphocytes were cultured with or without differentiation/pro-proliferative stimuli (Phorbol 12-Myristate 13-Acetate (PMA) alone or the combination of phytohaemagglutinin (PHA) with PMA, respectively), and the presence of MBI-eEF1A evaluated together with that of the eEF1A1/A2 mRNAs. Our data indicate that the MBI-eEF1A may derive from eEF1A1 as eEF1A2 is not expressed in CCRF-CEM and normal lymphocytes. Moreover, MBI-eEF1A is inducible in normal lymphocytes upon hyper-proliferative stimuli application; in CCRF-CEM, its presence can be abrogated by PMA-induced differentiation. Finally, MBI-eEF1A may have a functional role in hyper-proliferating/tumour cells as its disappearance reduces the growth of CCRF-CEM and that of PHA/PMA-stimulated lymphocytes. The presented data suggest that MBI-eEF1A may be related to oncogenic cell phenotype, rising the possibility to use MBI-eEF1A as target for novel therapeutic strategies.

show abstract

“…Due to the short length, miRNAs and siRNA can be easily chemically synthesized and used to target the mRNAs of genes causing disease. In this regard, there are several examples of the potential therapeutic value of miRNAs and siRNAs [107,108,109,110,111,112,113]. …”

Section: Polysaccharide-based Delivery Systems For Anti-cancer Drugsmentioning

confidence: 99%

Polysaccharides for the Delivery of Antitumor Drugs

et al. 2015

Self Cite

View full text Add to dashboard Cite

Among the several delivery materials available so far, polysaccharides represent very attractive molecules as they can undergo a wide range of chemical modifications, are biocompatible, biodegradable, and have low immunogenic properties. Thus, polysaccharides can contribute to significantly overcome the limitation in the use of many types of drugs, including anti-cancer drugs. The use of conventional anti-cancer drugs is hampered by their high toxicity, mostly depending on the indiscriminate targeting of both cancer and normal cells. Additionally, for nucleic acid based drugs (NABDs), an emerging class of drugs with potential anti-cancer value, the practical use is problematic. This mostly depends on their fast degradation in biological fluids and the difficulties to cross cell membranes. Thus, for both classes of drugs, the development of optimal delivery materials is crucial. Here we discuss the possibility of using different kinds of polysaccharides, such as chitosan, hyaluronic acid, dextran, and pullulan, as smart drug delivery materials. We first describe the main features of polysaccharides, then a general overview about the aspects ruling drug release mechanisms and the pharmacokinetic are reported. Finally, notable examples of polysaccharide-based delivery of conventional anti-cancer drugs and NABDs are reported. Whereas additional research is required, the promising results obtained so far, fully justify further efforts, both in terms of economic support and investigations in the field of polysaccharides as drug delivery materials.

show abstract

Effects of E2F1–cyclin E1–E2 circuit down regulation in hepatocellular carcinoma cells

Cited by 42 publications

References 37 publications

RNA-Seq Profiling Reveals Novel Hepatic Gene Expression Pattern in Aflatoxin B1 Treated Rats

RNA-Seq Profiling Reveals Novel Hepatic Gene Expression Pattern in Aflatoxin B1 Treated Rats

The more basic isoform of eEF1A relates to tumour cell phenotype and is modulated by hyper‐proliferative/differentiating stimuli in normal lymphocytes and CCRF‐CEM T‐lymphoblasts

Polysaccharides for the Delivery of Antitumor Drugs

Contact Info

Product

Resources

About