Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E2F family member of transcription factors includes the atypical member E2F8, which has been little studied in cancer. We report that E2F8 is strongly upregulated in human hepatocellular carcinoma (HCC), where it was evidenced to contribute to oncogenesis and progression. Ectopic overexpression of E2F8 promoted cell proliferation, colony formation, and tumorigenicity, whereas E2F8 knockdown inhibited these phenotypes, as documented in Huh-7, Focus, Hep3B, and YY-8103 HCC cell lines. Mechanistic analyses indicated that E2F8 could bind to regulatory elements of cyclin D1, regulating its transcription and promoting accumulation of S-phase cells. Together, our findings suggest that E2F8 contributes to the oncogenic potential of HCC and may constitute a potential therapeutic target in this disease.
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PMID:E2F8 contributes to human hepatocellular carcinoma via regulating cell proliferation. 2006 56

E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.
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PMID:E2F transcription factors and digestive system malignancies: how much do we know? 2511 Apr 51

In mammalian cells, E2F family of transcription factors (E2Fs) traditionally modulates assorted cellular functions related to cell cycle progression, proliferation, apoptosis and differentiation. Eight members, E2F1 E2F8 have been recognized of this family so far, and the members of this family are generally divided into activator E2F (E2F1--E2F3a), repressor E2F (E2F3b--E2F5) and inhibitor E2F (E2F6--E2F8) subclasses based on their structur-e and function. Studies have showed that the mammalian E2F family members represent a recent evolutionary adaptation to malignancies besides hepatocellular carcinoma (HCC), and a growing body of evidence has validated that the individual members of the family develop a close relationship with HCC. E2F1 was identified to play overlapping roles in HCC, while E2F2--E2F8 (except E2F6 and E2F7) showed to be tumor-promoter in HCC. However, the mechanism underlying the mammalian E2Fs associated with HCC is still unknown and needs further research. The aim of this review is to sum up the collective knowledge of E2F family and the roles of each member of this family in HCC. Moreover, we will discuss some novel therapeutic target for HCC based on the complicated functions of mammalian E2Fs.
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PMID:Promising roles of mammalian E2Fs in hepatocellular carcinoma. 2444 Mar 7

E2F-mediated transcriptional repression of cell cycle-dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8's tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8's DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development.
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PMID:E2f8 mediates tumor suppression in postnatal liver development. 2745 91

E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization. It also involves closely a variety of cellular physiological functions and pathological processes, which may bring a new breakthrough for the treatment of certain diseases, especially the HCC. Here, we summarize the latest progress of E2F8 on its relevant functions and mechanisms as well as potential application.
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PMID:E2F8 is a Potential Therapeutic Target for Hepatocellular Carcinoma. 2860 95

miR-223-5p has been demonstrated to regulate the development and progression of various cancers, such as hepatocellular carcinoma, breast cancer, and gastric carcinoma. However, the role of miR-223-5p in non-small cell lung cancer (NSCLC) requires further investigation. In this study, we found that the expression of miR-223-5p was significantly downregulated in NSCLC tissues and cell lines. Moreover, the expression level of miR-223-5p is negatively correlated with the malignance of NSCLC. We found that overexpression of miR-223-5p remarkably suppressed the proliferation of NSCLC cells in vitro and in vivo. miR-223-5p overexpression also led to reduced migration and invasion in NSCLC cells. Mechanistically, we found that E2F8, a key transcription factor involved in many kinds of biological processes, was a direct target gene of miR-223-5p. Overexpression of miR-223-5p significantly decreased the mRNA and protein levels of E2F8 in NSCLC cells. We also showed that restoration of E2F8 rescued the proliferation, migration, and invasion of miR-223-5p-overexpressing NSCLC cells. Taken together, our findings demonstrated that miR-223-5p suppressed NSCLC progression through targeting E2F8.
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PMID:miR-223-5p Suppresses Tumor Growth and Metastasis in Non-Small Cell Lung Cancer by Targeting E2F8. 2961 47

Cholangiocarcinoma (CCA) development is an extremely complex process with alterations occurring in numerous genes. SNHG6, a validated lncRNA, has been reported to regulate the expression of multiple tumor-related genes in hepatocellular carcinoma, colorectal cancer and breast cancer. Here, we elucidated the function and possible molecular mechanisms of SNHG6 in human CCA cells. Our results proved that the expression SNHG6 was upregulated in CCA tissues and cell lines. Ectopic expression of SNHG6 promoted cell proliferation, cell cycle progression, migration, and angiogenesis in CCA cells, whereas knockdown of SNHG6 repressed these cellular processes. Further mechanistic studies revealed that SNHG6 could compete with the transcription factor E2F8 to bind with miR-101-3p, thus affecting E2F8 expression. Taken together, these results provided a comprehensive analysis of the role of SNHG6 in CCA cells and offered important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human cholangiocarcinoma.
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PMID:Long noncoding RNA SNHG6 promotes proliferation and angiogenesis of cholangiocarcinoma cells through sponging miR-101-3p and activation of E2F8. 3222 15