FOXO transcription factors at the interface of metabolism and cancer

Link, Wolfgang; Fernández-Marcos, Pablo J.

doi:10.1002/ijc.30840

Cited by 88 publications

(66 citation statements)

References 213 publications

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“…FOX transcription factors are versatile proteins containing an evolutionarily conserved winged helix DNA-binding motif of about 100 residues at the N-terminal region, the forkhead (FKH) domain 2– 4 . FOXO3 belongs to the FOXO subclass (made of FOXO1, FOXO3, FOXO4, and FOXO6), which historically is known to regulate insulin signaling (comprehensively reviewed in 5, 6). Numerous regulatory processes, including phosphorylation, acetylation, ubiquitination, methylation 7, 8 , and microRNA (miRNA) binding 9 , can modulate FOXO3 transcriptional activity.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in understanding the role of FOXO3

et al. 2018

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The forkhead box O3 (FOXO3, or FKHRL1) protein is a member of the FOXO subclass of transcription factors. FOXO proteins were originally identified as regulators of insulin-related genes; however, they are now established regulators of genes involved in vital biological processes, including substrate metabolism, protein turnover, cell survival, and cell death. FOXO3 is one of the rare genes that have been consistently linked to longevity in in vivo models. This review provides an update of the most recent research pertaining to the role of FOXO3 in (i) the regulation of protein turnover in skeletal muscle, the largest protein pool of the body, and (ii) the genetic basis of longevity. Finally, it examines (iii) the role of microRNAs in the regulation of FOXO3 and its impact on the regulation of the cell cycle.

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Section: Introductionmentioning

confidence: 99%

Recent advances in understanding the role of FOXO3

et al. 2018

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“…The identification of these orchestrated functional changes is among the first step to unveil the little‐known embryonic programming and is important in enhancing our ability to improve our understanding of maternal function during the development of mammal embryo. For example, many transcription factors highly expressed in different stage during the development of embryo are important for cell proliferation, by regulating the transcription and replication of related genes, and it is similar to cell proliferation in cancer (Coomans de Brachene & Demoulin, ; Link & Fernandez‐Marcos, ).…”

Section: Discussionmentioning

confidence: 99%

Maternal transcription profiles at different stages for the development of early embryo in buffalo

Chen

et al. 2020

Reprod Domestic Animals

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Maternal mRNAs deposited in the egg during oogenesis are critical during the development of early embryo, before the activation of the embryonic genome. However, there is little known about the dynamic expression of maternally expressed genes in mammals. In this study, we made buffalo parthenogenesis as our research model to analyse maternal transcription profiles of pre-implantation embryo in buffalo using RNA sequencing. In total, 3,567 unique genes were detected to be differentially expressed among all constant stages during early embryo development (FPKM > 0).Interestingly, a total of 10,442 new genes were discovered in this study, and gene ontology analysis of the new differentially expressed genes indicated that the new genes have a wide cellular localization and are involved in many molecular functions and biological processes. Moreover, we identified eight clusters that were only highly expressed in a particular developmental stage and enriched a number of GO terms and KEGG pathways that were related to specific stage. Furthermore, we identified 1,530 hub genes (or key members) from the maternally expressed gene networks, and these hub genes were involved in 11 stage-specific modules. After visualization using Cytoscape 3.2.1 software, we obtained complex interaction network of hub genes, indicating the highly efficient cooperation between genes during the development in buffalo embryos. Further research of these genes will greatly deepen our understanding of embryo development in buffalo. Collectively, this research lays the foundation for future studies on the maternal genome function, buffalo nuclear transfer and parthenogenetic embryonic stem cells.

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“…Forkhead TFs are well known to play pivotal roles in regulating various cellular behaviors. 13,25 For the first time, the Forkhead family member, FOXM1, was identified as a novel mechanosensitive gene in human PDLCs. This study demonstrated that suppression of FOXM1 in PDLCs promoted the osteoclastogenesis of cocultured RAW264.7 cells, implying that force-induced FOXM1 reduction contributed to osteoclast differentiation ( Figure 2).…”

Section: Targetmentioning

confidence: 99%

Force-induced decline of FOXM1 in human periodontal ligament cells contributes to osteoclast differentiation

Zhang

Liu

et al. 2019

The Angle Orthodontist

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Objectives: To investigate whether Forkhead family transcription factors are responsive to mechanical force and the resulting influence on the osteoclast differentiation mediated by human periodontal ligament cells (PDLCs). Materials and Methods: A high-throughput RNA sequencing assay was performed in compressive force–stimulated and control human PDLCs. Alteration of FOXM1, a member of the Forkhead family transcription factors, was further confirmed by Western blotting and quantitative reverse-transcription polymerase chain reaction. Expression of FOXM1 was inhibited by either small interfering RNA (siRNA) transfection or addition of its specific inhibitor Siomycin A. Then, cells were exposed to compressive force and co-cultured with the murine macrophage cell line Raw264.7, followed by tartrate-resistant acid phosphatase staining assay. Expression changes of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegetin (OPG) caused by FOXM1 suppression were measured. Alkaline phosphatase (ALP) staining, ALP activity assay, and crystal violet staining assay were performed after FOXM1 inhibition. Results: FOXM1 transcription decreased after mechanical stimulation in PDLCs. Inhibition of FOXM1 promoted force-induced osteoclast differentiation of RAW264.7 and upregulated the RANKL/OPG ratio in PDLCs. Interference of FOXM1 led to promoted osteogenic differentiation but decreased proliferation of PDLCs. Conclusions: FOXM1 is a novel mechano-responsive gene in human PDLCs. Suppressing FOXM1 expression could promote osteoclast differentiation as well as RANKL/OPG in human PDLCs. FOXM1 also plays a role in controlling PDLC differentiation and proliferation capacity.

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FOXO transcription factors at the interface of metabolism and cancer

Cited by 88 publications

References 213 publications

Recent advances in understanding the role of FOXO3

Recent advances in understanding the role of FOXO3

Maternal transcription profiles at different stages for the development of early embryo in buffalo

Force-induced decline of FOXM1 in human periodontal ligament cells contributes to osteoclast differentiation

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