Together, our study firstly confirmed a potential synergy between KRAS and MDM4/E2F1 which are p53/RB inactivators in non-small cell lung cancer, and identified miR-1205 as a potent destructor of this synergy, making miR-1205 function as a tumor suppressor in vitro and in vivo.
The transcription factor, E2 promoter binding factor 1 (E2F-1), exhibits tumor promoter or suppressive functions depending on cellular type and tissue context, but its role in the progression and development of colorectal carcinogenesis was largely unknown.
The mRNA expression levels of <i>E2F1/3/5/8</i> were found to be significantly upregulated in patients with OC and were obviously associated with tumor stage for OC.
In HCC specimens, E2F1 expression was much higher in tumor than in non-tumor tissues, and was significantly related to Edmondson-Steiner grade, overall as well as tumor-free survival.
Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor <i>RB1</i> VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway.
If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53 axis were the same as those experimentally demonstrated in mouse models, the disruption of this axis might be useful to predict tumor aggressiveness, and to provide the basis towards the development of potential therapeutic strategiesin human T-LBL.
In a Western blot analysis of GOT1 cells, NVP-CGM097 caused a dose-dependent increase in the expression of p53 and p21 tumor suppressor proteins and a decrease in phospho-Rb and E2F1.
No EZH2 mutations were detected, however, overexpression of c-Myc, E2F1 and pRb proteins as well as reduced expression of the tumor suppressor miR-26a were demonstrated in the PCs.
ARTD treatment induced the expression of tumor suppressive activating transcription factor 3 and inhibited oncogenic E2F transcription factor 1 expression at the mRNA and protein levels.
Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients.
E2F1-3a overexpression due to amplification or to mutation or loss of the retinoblastoma gene, induces genes involved in DNA synthesis and leads to abnormal cellular proliferation, tumor growth, and invasion.
Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models.
Knowledge analysis demonstrates our E2F1 feedback-interactive BRCA1 pathway wide disease distribution and reflects a novel common one of tumor and cancer.
Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells.
Our integrative network-based methodology, exemplified in the case of E2F1-induced aggressive tumors, has the potential to support the design of cohort- as well as tumor type-specific treatments and ultimately, to fight metastasis and therapy resistance.Deregulation of E2F family transcription factors is associated with cancer progression and metastasis.
In this study, integrated analysis revealed that E2F1 expression was significantly increased in GC cases and its expression was positively correlated with the poor pathologic stage, large tumor size and poor prognosis.
Thus, we hypothesized that a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) was associated with risk of oral squamous cell carcinoma (OSCC) and tumor HPV status of oropharynx squamous cell carcinoma (OPSCC).
Our data support a model in which iAs inhibits the dissociation of E2F1 from the tumor suppressor, retinoblastoma protein (pRB) due to changes in pRB phosphorylation which leads to decreased E2F1 transcriptional activity.
E2F1 is reported to be overexpressed in several types of human tumors and its inactivation may be a valuable novel potential therapeutic strategy for cancer treatment.
E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue.