FOXO1 inhibits osteosarcoma oncogenesis via Wnt/β-catenin pathway suppression

Guan, Hanfeng; Tan, Peng; Xie, Linka; Mi, Bobin; Fang, Zhong; Li, J; Yue, Junqiu; Liao, Hui; Li, F

doi:10.1038/oncsis.2015.25

Cited by 56 publications

(59 citation statements)

References 47 publications

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“…Evidence indicates that Wnt/β‐catenin signaling pathway involves in maintenance and development of many tissues and organs, including bone . In fact, most OS cases are found to show β‐catenin overexpression and elevated nuclear localization, which is correlated with lung metastasis . In view of the complex regulatory role of miR‐940, it is necessary to explore its regulatory role in different disease models.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Lin

Zhang

Jiang

et al. 2018

J of Cellular Biochemistry

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Osteosarcoma (OS) is the most common malignant tumor of bone with a high potential for metastasis. This study intends to explore whether microRNA‐940 (miR‐940) affects the development of OS cells and the underlying mechanism. OS and adjacent normal tissues were collected from OS patients; the OS cell line with the highest expression of miR‐940 was selected, which was then subjected to transfection of miR‐940 mimic, miR‐940 inhibitor, siRNA‐secreted frizzled‐related protein 1 (SFRP1) or LiCl (agonists of Wnt/β‐catenin pathway) to identify regulation of miR‐940 to OS cells through SFRP1. The targeting relationship between miR‐940 and SFRP1 was verified using dual‐luciferase reporter gene assay. Reverse‐transcription quantitative polymerase chain reaction and Western blot assay were performed to determine miR‐940, SFRP1, β‐catenin, and cyclinD1 and apoptosis‐related genes Fas, Bax, and Bcl‐2. MTT (3‐(4, 5‐dimethylthiazol‐2‐Yl)‐2, 5‐diphenyltetrazolium bromide) assay, scratch test, transwell assay, and flow cytometry were carried out to detect proliferation, migration, invasion, and apoptosis, respectively. Nude mice models were established to observe the tumor formation. Higher expression of miR‐940, β‐catenin, and cyclinD1 and lower SFRP1 expression were identified in OS tissues. miR‐940 targeted and negatively regulated SFRP1 expression. Furthermore, upregulated miR‐940 expression activated the Wnt/β‐catenin signaling pathway in OS. With the treatment of miR‐940 mimic, LiCL, or siRNA‐SFRP1, OS cells showed promoted proliferation, migration, invasion, tumor formation, and impeded apoptosis (further reflected by elevated Bcl‐2 expression and reduced Fas and Bax expression). The study demonstrates that miR‐940 can promote the proliferation, migration, and invasion but suppress the apoptosis of human OS cells by downregulating SFRP1 through activating Wnt/β‐catenin signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Lin

Zhang

Jiang

et al. 2018

J of Cellular Biochemistry

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“…By reducing FOXO1 nuclear localization, GnRH could thus enhance the transactivation capacity of SF1, β-catenin, and Egr1. The ability of FOXO1 to inhibit Wnt/β-catenin signaling has recently been reported in osteoblast precursors as well as in sarcoma cell lines [58, 59], which supports this hypothesis. The underlying molecular mechanisms of this phenomenon are still to be determined.…”

Section: Discussionsupporting

confidence: 62%

GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells

et al. 2018

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Background/Objectives: Anti-Müllerian hormone (AMH) signaling is critical for sexual differentiation and gonadal function. AMH receptor type 2 (AMHR2) is expressed in extragonadal sites such as brain, and pituitary and emerging evidence indicates that AMH biological action is much broader than initially thought. We recently reported that AMH signaling enhances follicle-stimulating hormone synthesis in pituitary gonadotrope cells. However, mechanisms regulating AMHR2 expression in these extragonadal sites remain to be explored. Method/Results: Here, we demonstrated in perifused murine LβT2 gonadotrope cells that Amhr2 expression is differentially regulated by GnRH pulse frequency with an induction under high GnRH pulsatility. Furthermore, we showed that GnRH transactivates the human AMHR2 promoter in LβT2 cells. Successive deletions of the promoter revealed the importance of a short proximal region (–53/–37 bp) containing an Egr1 binding site. Using site-directed mutagenesis of Egr1 motif and siRNA mediated-knockdown of Egr1, we demonstrated that Egr1 mediates basal and GnRH-dependent activity of the promoter, identifying Egr1 as a new transcription factor controlling hAMHR2 expression. We also showed that SF1 and β-catenin are required for basal promoter activity and demonstrated that both factors contribute to the GnRH stimulatory effect, independently of their respective binding sites. Furthermore, using a constitutively active mutant of FOXO1, we identified FOXO1 as a negative regulator of basal and GnRH-dependent AMHR2 expression in gonadotrope cells. Conclusions: This study identifies GnRH as a regulator of human AMHR2 expression, further highlighting the importance of AMH signaling in the regulation of gonadotrope function.

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“…45, 46, 47 Thus, FoxO1 may regulate osteogenic differentiation by competing with the TCF/LEF complex for β -catenin and inhibiting the canonical Wnt pathway. Our results are in support of our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients

Wang¹,

Song

et al. 2016

Cell Death Dis

146

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Periodontitis impairs the osteogenic differentiation of human periodontal mesenchymal stem cells (hPDLSCs), but the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to have significant roles under both physiologic and pathological conditions. In this study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified a novel lncRNA, osteogenesis impairment-related lncRNA of PDLSCs from periodontitis patients (lncRNA-POIR), the expression of which was significantly decreased in PDLSCs from periodontitis patients (pPDLSCs) and was upregulated by osteogenic induction. To study the functions of lncRNA-POIR, we prepared cells with overexpression and knockdown of lncRNA-POIR and found that lncRNA-POIR positively regulated osteogenic differentiation of hPDLSCs and pPDLSCs both in vitro and in vivo. Using quantitative real-time PCRs (qPCRs) and luciferase reporter assays, we demonstrated that lncRNA-POIR may act as a competing endogenous RNA (ceRNA) for miR-182, leading to derepression of its target gene, FoxO1. In this process, lncRNA-POIR and miR-182 suppress each other and form a network to regulate FoxO1. FoxO1 increased bone formation of pPDLSCs by competing with TCF-4 for β-catenin and inhibiting the canonical Wnt pathway. Finally, inflammation increases miR-182 expression through the nuclear factor-κB pathway, and the miR-182 overexpression in the inflammatory microenvironment resulted in an imbalance in the lncRNA-POIR-miR-182 regulatory network. In conclusion, our results provide novel evidence that this lncRNA-miRNA (microRNA) regulatory network has a significant role in osteogenic differentiation of pPDLSCs and that it has potential as a therapeutic target in mesenchymal stem cells during inflammation.

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FOXO1 inhibits osteosarcoma oncogenesis via Wnt/β-catenin pathway suppression

Cited by 56 publications

References 47 publications

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells

Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients

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