E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

Castillo, Del; Campalans, Anna; Belluscio, Laura María; Carcagno, Abel L.; Radicella, J. Pablo; Cánepa, Eduardo T.; Pregi, Nicolás

doi:10.4161/15384101.2014.985031

Cited by 26 publications

(23 citation statements)

References 67 publications

(77 reference statements)

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“…Similarly, AKT3 may be an important target gene of miRNA-195. From the functions annotated in the genes E2F1 and E2F2 in GO, we can speculate that the genes E2F1 and E2F2 are present on the nucleoplasm, and participate in the lens fiber cell apoptosis process or intrinsic apoptotic signaling pathway by p53 class mediator by forming a complex with a certain protein or transcription factor activity, sequence-specific DNA binding, which is consistent with the results reported previously (Castillo et al, 2015). In addition, PI3K-Akt and AMPK are reported to be positive and negative regulators of mTOR activity, respectively, and mTOR is a well-known sensor for extracellular nutrients and growth factors, which converges many key signals and is widely involved in cell cycle, cell proliferation, and cellular metabolic processes, and has important biological roles in regulating apoptosis, physiological, and pathological processes (Ciuffreda et al, 2010).…”

Section: Functional Analysissupporting

confidence: 91%

Identification of the Key Factors Related to Bladder Cancer by lncRNA-miRNA-mRNA Three-Layer Network

et al. 2020

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Bladder cancer is the most common malignant tumor of the urinary system, and it has high incidence, high degree of malignancy, and easy recurrence after surgery. The etiology and pathogenesis of bladder cancer are not fully understood, but more and more studies have shown that its development may be regulated by some core molecules. To identify key molecules in bladder cancer, we constructed a three-layer network by merging lncRNA-miRNA regulatory network, miRNA-mRNA regulatory network, and lncRNA-mRNA coexpression network, and further analyzed the topology attributes of the network including the degree, betweenness centrality and closeness centrality of nodes. We found that miRNA-93 and miRNA-195 are controllers for a three-layer network and regulators of numerous target genes associated with bladder cancer. Functional enrichment analysis of their target mRNAs revealed that miRNA-93 and miRNA-195 may be closely related to bladder cancer by disturbing the homeostasis of the cell cycle or HTLV-I infection. In addition, since E2F1 and E2F2 are enriched in various KEGG signaling pathways, we conclude that they are important target genes of miRNA-93, and participate in the apoptotic process by forming a complex with a certain protein or transcription factor activity, sequence-specific DNA binding in bladder cancer. Similarly, AKT3 is an important target gene of miRNA-195, its expression is associated with PI3K-Akt-mTOR signaling pathway and AMPK-mTOR signaling pathway. Therefore, we speculate that AKT3 may participate in proliferation and apoptosis of bladder cancer cells through these pathways, and ultimately affect the biological behavior of tumor cells. Furthermore, through survival analysis, we found that miRNA-195 and miRNA-93 are associated with poor prognosis of bladder cancer. And the Kaplan-Meier curve showed that 24 mRNAs and nine lncRNAs are closely related to overall survival of bladder cancer.

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Section: Functional Analysissupporting

confidence: 91%

Identification of the Key Factors Related to Bladder Cancer by lncRNA-miRNA-mRNA Three-Layer Network

et al. 2020

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“…This phenomenon seems to be cell context dependent and may play a role in neurodegeneration (51). Furthermore, E2f2 and E2F1 were reported to provide genomic stability in some neurons in the context of DNA damage (52). This study additionally showed accumulation of E2f2 protein levels, despite unchanged transcription.…”

Section: Discussionsupporting

confidence: 54%

Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

Judd

Lovas

Huang

2019

Preprint

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Adult mammalian cardiomyocytes exit the cell cycle during the neonatal period, commensurate with the loss of regenerative capacity in adult mammalian hearts. We established conditions for long-term culture of adult mouse cardiomyocytes that are genetically labeled with fluorescence. This technique permits reliable analyses of proliferation of pre-existing cardiomyocytes without complications from cardiomyocyte marker expression loss due to dedifferentiation or significant contribution from cardiac progenitor cell expansion and differentiation in culture.Using this system, we took a candidate gene approach to screen for fetal-specific proliferative gene programs that can induce proliferation of adult mouse cardiomyocytes. Using pooled gene delivery and subtractive gene elimination, we identified a novel functional interaction between E2f Transcription Factor 2 (E2f2) and Brain Expressed X-Linked (Bex)/Transcription elongation factor A-like (Tceal) superfamily members Bex1 and Tceal8. Specifically, Bex1 and Tceal8 both preserved cell viability during E2f2-induced cell cycle re-entry. Although Tceal8 inhibited E2f2-induced S-phase re-entry, Bex1 facilitated DNA synthesis while inhibiting cell death. In sum, our study provides a valuable method for adult cardiomyocyte proliferation research and suggests that Bex family proteins may function in modulating cell proliferation and death decisions during cardiomyocyte development and maturation.Real-time PCR showed that expression of endogenous positive cell cycle regulators Cyclin A2 and Cyclin E were induced by ectopic E2f2 expression, in agreement with

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“…The role of E2fs in mitosis has been shown in cancer cells [59–63]. Although the specific function of E2f2 in response to radiation has not been studied, E2f2 transcript and protein levels increase in response to genotoxic stress and maintain genomic stability in neuronal cells [64]. Why E2f2 shows bi-directional expression changes, whereas other E2f members (i.e., E2f1 , E2f3 , E2f4 , and E2f8 ) do not, is currently not known.…”

Section: Discussionmentioning

confidence: 99%

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Broustas

Harken

et al. 2017

BMC Genomics

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BackgroundIn the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of photons plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in a more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions.ResultsMice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7285 and 5045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7.ConclusionsWe describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3436-1) contains supplementary material, which is available to authorized users.

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E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

Cited by 26 publications

References 67 publications

Identification of the Key Factors Related to Bladder Cancer by lncRNA-miRNA-mRNA Three-Layer Network

Identification of the Key Factors Related to Bladder Cancer by lncRNA-miRNA-mRNA Three-Layer Network

Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

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