Downregulation of <scp>DEC</scp>1 contributes to the neurotoxicity induced by <scp>MPP</scp><sup>+</sup> by suppressing <scp>PI</scp>3K/Akt/<scp>GSK</scp>3β pathway

Zhu, Zhu; Wang, Yuwen; Dinghao, Ge; Lu, Ming; Liu, Wei; Xiong, Jing; Hu, Gang; Li, Xiaoping; Yang, Jian

doi:10.1111/cns.12717

Cited by 18 publications

(22 citation statements)

References 61 publications

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“…It has been revealed that DEC1 overexpression and knockdown inversely regulate the expression levels of β-catenin and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α in glucocorticoid-induced osteoporotic changes in SaoS-2 cells and mice ( 17 ). Furthermore, downregulation of DEC1 contributes to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by suppressing the PI3K/Akt/glycogen synthase kinase 3 β (GSK-3β) pathway ( 18 ). The Wnt/β-catenin signaling pathway is one of the most important signal transduction pathways in cells, and serves an essential role in regulating normal cell proliferation, movement, differentiation and tumorigenesis ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β‑catenin signaling pathway

Liao

Zheng

et al. 2021

Exp Ther Med

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DEC1 has been reported to regulate the expression of multiple target genes, participate in cell differentiation, apoptosis, aging and the development and progression of numerous tumors, but the detailed effects and possible mechanisms of DEC1 in ovarian cancer (OC) remain unknown. The present study aimed to investigate the expression and mechanism of function of DEC1 in OC. The present results demonstrated that DEC1 was highly expressed in OC tissues and cell lines using reverse transcription-quantitative PCR, western blotting and immunohistochemistry, and high expression of DEC1 was negatively associated with the prognosis of patients with OC. In addition, knockdown of DEC1 significantly inhibited proliferation in SKOV3 and OVCAR3 cells compared with control. DEC1 knockdown also induced apoptosis and increased the expression of apoptosis-related proteins in OC cells. The results suggested that knockdown of DEC1 inhibited OC cell migration and invasion via regulation of epithelial-mesenchymal transition-related protein. It was also found that DEC1 knockdown significantly inhibited the Wnt/β-catenin pathway. Collectively, the current results indicated that knockdown of DEC1 inhibited proliferation, migration and invasion, and induced apoptosis in OC cells via modulating the Wnt/β-catenin signaling pathway. Thus, DEC1 may participate in malignant progression of OC, and may be a target for treatment and diagnosis of OC.

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Section: Introductionmentioning

confidence: 99%

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β‑catenin signaling pathway

Liao

Zheng

et al. 2021

Exp Ther Med

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“…Previous studies have reported that DEC1 can be induced in a cell type-specific manner by various extracellular stimuli, such as hypoxia, growth factors, hormones and cytokines (35)(36)(37)(38). DEC1 can also act as a transcriptional factor through interactions with the PI3K/Akt/glycogen synthase kinase 3β signaling pathway to promote osteogenic activity and to relieve 1-methyl-4-phenylpyridinium-induced cytotoxicity (39,40). A recent study showed that activation of the Akt/P53/P21 signaling pathway promotes proliferation and migration of human osteosarcoma cells, and activation of the Akt/P53/P21 signaling pathway induced the downregulation of DEC1 (21); however, the direct effect of DEC1 on regulating the Akt/P53/P21 signaling pathway remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Effect of DEC1 on the proliferation, adhesion, invasion and epithelial‑mesenchymal transition of osteosarcoma cells

Peng

Yin

et al. 2020

Exp Ther Med

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Differentiated embryonic chondrocyte-expressed gene 1 (DEC1) is associated with various types of human cancer; however, there is limited data regarding the functions of DEC1 in osteosarcoma. The present study aimed to examine the expression of DEC1 in human osteosarcoma tissues and cell lines. Furthermore, the effects of DEC1 on the proliferation, adhesion, invasion and epithelial-mesenchymal transition (EMT) of osteosarcoma cells were investigated. Using reverse transcription-quantitative PCR and western blot analysis, it was found that the expression levels of DEC1 were higher in human osteosarcoma tissues and osteosarcoma cell lines than in the controls. Both gain-and loss-of-function experiments suggested that DEC1 promotes the proliferation, adhesion and invasion of osteosarcoma cells in vitro, as determined by MTT, cell adhesion and cell invasion assays, respectively. Additionally, DEC1 was found to upregulate the mesenchymal markers N-cadherin and vimentin, whilst downregulating the epithelial marker E-cadherin. In conclusion, this present study showed increased expression levels of DEC1 in human osteosarcoma tissues and cell lines, and identified that DEC1 may exert its effect on osteosarcoma progression by promoting cell proliferation, adhesion and invasion. Furthermore, DEC1 was shown to have an inducible effect on EMT in osteosarcoma cell lines, thus contributing to the aggressiveness of osteosarcoma cells. This initial study indicated that DEC1 may serve as a novel molecular target for the treatment of osteosarcoma.

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“…MiR-30a-5p regulated GLT-1 through the PKCα pathway in the SNpc of MPTP-treated mice Since we found that GLT-1 expression and function was indeed regulated by miR-30a-5p but that Slc1a2 was not a target gene of miR-30a-5p, we hypothesized that miR-30a-5p regulates GLT-1 via an undetermined pathway. As potential intermediaries between miR-30a-5p and GLT-1, we chose several signaling molecules that have been associated with PD, namely PI3K, PKCα, STAT3, and mTOR [50][51][52][53][54]. As expected from their known roles in PD, western blots of the active, phosphorylated (p-) form of these proteins showed that PI3K (p < 0.01) (Fig.…”

Section: Mir-30a-5p Regulated the Expression And Function Of Glt-1 In Vitromentioning

confidence: 99%

MiR-30a-5p Regulates GLT-1 Function via a PKCα-Mediated Ubiquitin Degradation Pathway in a Mouse Model of Parkinson’s Disease

Meng

Zhong

Zeng

et al. 2021

ACS Chem. Neurosci.

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Background:Glutamate excitotoxicity caused by dysfunctional glutamate transporters plays an important role in the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not fully elucidated. MicroRNAs have been reported to play key roles in regulating the translation of glutamate-transporter mRNA.Methods: We established model of PD 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice in vivo and 1-methyl-4-phenylpyridinium (MPP + ) treated astrocyte in vitro. Stereotaxic injection of shRNA in mouse, and miRNA inhibitor/mimic, or antagonist/agonist treated the cell model, Behavioral experiments, glutamic acid uptake, transport activity of synaptosomes, underlying mechanisms and the impact on neuronal survival were assessed. ResultsWe demonstrated that short-hairpin RNA-mediated knockdown of miR-30a-5p ameliorated motor de cits and pathological changes like astrogliosis and reactive microgliosis in a mouse model of PD. Western blotting and immuno uorescent labeling revealed that miR-30a-5p suppressed the expression and function of GLT-1 in MPTP-treated mice and speci cally in astrocytes treated with (cell model of PD).Conclusion Both in vitro and in vivo, we found that miR-30a-5p knockdown promoted glutamate uptake and increased GLT-1 expression by hindering GLT-1 ubiquitination and subsequent degradation in a PKCα-dependent manner. Therefore, miR-30a-5p represents a potential therapeutic target for the treatment of PD. BackgroundParkinson's disease (PD) is an age-associated movement disorder whose pathological hallmark is the progressive death of dopaminergic cells in the substantia nigra pars compacta (SNpc) coupled with the accumulation of Lewy bodies containing alpha-synuclein (α-Syn) [1]. Several different mechanisms are believed to contribute to the death of dopaminergic (DA) neurons in PD, including genetic factors [2-5], environmental factors [6,7], neuroin ammation [8-10] and glutamate excitotoxicity [11][12][13][14][15][16]. The role of glutamate excitotoxicity in the development of PD has become increasingly important in recent years. Glutamate transporters play a predominant role in clearing excess glutamate from the synaptic cleft. Five mammalian excitatory-amino-acid transporters (EAATs) have been characterized: glutamate/aspartate transporter (GLAST, also called EAAT1), glutamate transporter-1 (GLT-1, also called EAAT2), excitatory amino acid carrier-1 (EAAC1, also called EAAT3), EAAT4, and EAAT5[17-23. Among the glutamate transporters, GLT-1, found on astrocytes, is the most critical in the development of PD because it is responsible for the uptake of nearly 90% of synaptic glutamate [14,24].Based on our previous studies, upregulation of GLT-1 could signi cantly improve the motor de cits and pathological changes in mice treated with 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) [14,15]. We showed that rapamycin and Nedd4-2 knockdown ameliorated movement abnormalities in a PD mouse model and increased t...

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Downregulation of DEC1 contributes to the neurotoxicity induced by MPP⁺ by suppressing PI3K/Akt/GSK3β pathway

Abstract: Downregulation of DEC1 contributes to MPP -induced neurotoxicity by suppressing PI3K/Akt/GSK3β pathway.

Cited by 18 publications

References 61 publications

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β‑catenin signaling pathway

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β‑catenin signaling pathway

Effect of DEC1 on the proliferation, adhesion, invasion and epithelial‑mesenchymal transition of osteosarcoma cells

MiR-30a-5p Regulates GLT-1 Function via a PKCα-Mediated Ubiquitin Degradation Pathway in a Mouse Model of Parkinson’s Disease

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Downregulation of DEC1 contributes to the neurotoxicity induced by MPP+ by suppressing PI3K/Akt/GSK3β pathway

Abstract: Downregulation of DEC1 contributes to MPP -induced neurotoxicity by suppressing PI3K/Akt/GSK3β pathway.

Cited by 18 publications

References 61 publications

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β‑catenin signaling pathway

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β‑catenin signaling pathway

Effect of DEC1 on the proliferation, adhesion, invasion and epithelial‑mesenchymal transition of osteosarcoma cells

MiR-30a-5p Regulates GLT-1 Function via a PKCα-Mediated Ubiquitin Degradation Pathway in a Mouse Model of Parkinson’s Disease

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Downregulation of DEC1 contributes to the neurotoxicity induced by MPP⁺ by suppressing PI3K/Akt/GSK3β pathway