Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

Foronda, Miguel; Martínez, Paula; Schoeftner, Stefan; Gómez‐López, Gonzalo; Schneider, Ralph P.; Flores, Juana M.; Pisano, David G.; Blasco, Marı́a A.

doi:10.1016/j.celrep.2014.06.031

Cited by 53 publications

(40 citation statements)

References 82 publications

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“…Mirroring the neuronal system (27), our studies established pancreatic SOX4 as a factor that initially specifies a terminally differentiated b-cell state (8) and then supports b-cell proliferation. This is in agreement with experimental evidence that SOX4 can act as an oncogene (28) as well as regulate cell-cycle genes and proliferation (29,30).…”

Section: Discussionsupporting

confidence: 92%

SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a

Sasaki

Speckmann

et al. 2017

Diabetes

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The high-mobility group box transcription factor SOX4 is the most highly expressed SOX family protein in pancreatic islets, and mutations in are associated with an increased risk of developing type 2 diabetes. We used an inducible β-cell knockout mouse model to test the hypothesis that is essential for the maintenance of β-cell number during the development of type 2 diabetes. Knockout of at 6 weeks of age resulted in time-dependent worsening of glucose tolerance, impairment of insulin secretion, and diabetes by 30 weeks of age. Immunostaining revealed a decrease in β-cell mass in knockout mice that was caused by a 39% reduction in β-cell proliferation. Gene expression studies revealed that induction of the cell cycle inhibitor was responsible for the decreased proliferation in the knockout animals. Altogether, this study demonstrates that SOX4 is necessary for adult β-cell replication through direct regulation of the β-cell cycle.

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Section: Discussionsupporting

confidence: 92%

SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a

Sasaki

Speckmann

et al. 2017

Diabetes

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“…The promoter regions of the "late" period hubs are enriched in DNA binding motifs for E2F, ETS, GATA, the Wnt/β-catenin effectors (TCF/Myc), and Sox family proteins ( Figure 5A,B). These data are consistent with the downregulation of proliferation-related genes (E2F, ETS) ( Figures 2 and 3C,D), the acquisition of more differentiated and aging features (GATA, Sox, Wnt) [35][36][37][38] (Figure 4C), and the upregulation of Wnt/β-catenin gene signatures observed in our previous in silico analyses (Figure 3C,D; cluster "b"). However, given that the Myc gene signatures are downmodulated in this period (Figure 3C,D; cluster "f"), it is likely that the Wnt target genes could be regulated by either TCF proteins or other transcriptional factors working downstream of Wnt.…”

Section: Identification Of Transcriptional Factors Potentially Involvsupporting

confidence: 89%

In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells

Lorenzo‐Martín

Bustelo

2020

Cells

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The stem cells located in the hair follicle bulge area are critical for skin regeneration and repair. To date, little is known about the evolution of the transcriptome of these cells across time. Here, we have combined genome-wide expression analyses and a variety of in silico tools to determine the age-dependent evolution of the transcriptome of those cells. Our results reveal that the transcriptome of skin stem cells fluctuates extensively along the lifespan of mice. The use of both unbiased and pathway-centered in silico approaches has also enabled the identification of biological programs specifically regulated at those specific time-points. It has also unveiled hubs of highly transcriptionally interconnected genes and transcriptional factors potentially located at the core of those age-specific changes.

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“…In recent years, a number of studies have suggested that SOX4 may be associated with tumour development and progression (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

lncRNA XIST promotes glioma proliferation and metastasis through miR‑133a/SOX4

et al. 2020

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Glioma is the most common malignant brain tumour in adults, and the aetiology and mechanism of this tumour remain largely unknown. Previous studies have demonstrated that the long non-coding RNA X-inactive specific transcript (XIST) is upregulated in many cancers, and a high expression level of XIST is associated with poor clinical outcome. In the present study, the expression and function of XIST were investigated in the glioma cell line U251. XIST and microRNA (miR)-133a levels in glioma cell lines were detected by reverse transcription-quantitative polymerase chain reaction. Small hairpin RNA XIST (sh-XIST) and mimics/inhibitor of miR-133a were transfected in glioma cell lines and cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) were examined. Luciferase assays were used to verify the associations among XIST, miR-133a and SRY-box (SOX)4. When XIST was knocked down, the proliferation, metastasis and EMT of glioma cells decreased. Notably, downstream genes of SOX4 were also upregulated or downregulated upon sh-XIST treatment. Overexpression of miR-133a inhibited glioma proliferation, metastasis and EMT via reducing the expression of SOX4; in contrast, knockdown of miR-133a exhibited the opposite effect, which revealed that miR-133a negatively regulates glioma progression. Furthermore, using luciferase assays, it was demonstrated that XIST and SOX4 could bind miR-133a in the predicted binding site; XIST competed with SOX4 for miR-133a binding. In conclusion, a XIST/miR-133a/SOX4 axis and a mechanism of XIST glioma in promoting cell proliferation and metastasis were revealed. These findings revealed that XIST has an oncogenic role in the tumourigenesis of glioma and may serve as a potential therapeutic target for glioma.

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Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

Cited by 53 publications

References 82 publications

SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a

SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a

In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells

lncRNA XIST promotes glioma proliferation and metastasis through miR‑133a/SOX4

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