The lncRNA CASC2/miR-18b/RORA Axis Suppresses Invasion and the Epithelial-Mesenchymal Transition in Multifocal Glioblastomas via the TGF-β1 /Smad Signaling Pathway

2020 ◽  
Author(s):  
Junshuang Zhao ◽  
Yang Jiang ◽  
Haiying Zhang ◽  
Jinpeng Zhou ◽  
Hao Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

scholarly journals Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Haiyan Xu ◽  
Xu Wang ◽  
Mingming Liu ◽  
Xueyuan He
Keyword(s):  
Molecular Markers ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Rats ◽  
High Dose ◽  
Mesenchymal Transition ◽  
Dose Treatment ◽  
Smad Signaling ◽  
Smad Signaling Pathway

This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT) related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

scholarly journals DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

Oncotarget ◽  
2016 ◽  
Vol 7 (47) ◽  
pp. 77306-77318 ◽  
Author(s):  
Yan-Ping Liu ◽  
Hui-Fang Zhu ◽  
Ding-li Liu ◽  
Zhi-Yan Hu ◽  
Sheng-Nan Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway

scholarly journals Effects of Astragaloside IV Against the TGF-β1-Induced Epithelial-to-Mesenchymal Transition in Peritoneal Mesothelial Cells by Promoting Smad 7 Expression

2015 ◽  
Vol 37 (1) ◽  
pp. 43-54 ◽  
Author(s):  
Lu Zhang ◽  
Zhenghong Li ◽  
Weiming He ◽  
Lingdong Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Treated Group ◽  
Mesothelial Cells ◽  
Vehicle Group ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Peritoneal Mesothelial Cells ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Background/Aims: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the TGF-β1/Smad signaling pathway in peritoneal mesothelial cells with an epithelial-to-mesenchymal transition (EMT). Methods: EMT of human peritoneal mesothelial cells (HMrSV5) was induced using 2 ng/ml TGF-β1. Cells were randomly divided into a vehicle group, a vehicle group with AS-IV, a TGF-β1 treated group, and a TGF-β1 treated group receiving varied doses of AS-IV or NAC. Real-time quantitative PCR and western blot were used to detect the expression of genes and proteins associated with the TGF-β1/Smad signaling pathway and EMT. DCFH-DA was used to detect the generation of ROS in HMrSV5 cells, and a transwell migration assay was used to verify the capacity of AS-IV to inhibit EMT in HMrSV5 cells. Lentiviruses were used as carriers for the overexpression or knockdown of the Smad7 gene. Results: Expression levels of E-cadherin (epithelial marker) was decreased and vimentin, α-SMA (EMT markers) and collagen I (extracellular matrix protein) phospho-Smad2/3, Snail1 and Snail2 was increased significantly in the TGF-β1-treated HMrSV5 cells. AS-IV was associated with downregulated expression of vimentin and phospho-Smad2/3 in a dose-dependent manner, while the expression of Smad7 increased. Silenced or forced expression of Smad7 verified its role in the inhibitory effect of AS-IV on TGF-β1-induced EMT in HMrSV5 cells. Conclusion: AS-IV effectively promotes the upregulation of Smad7 in the TGF-β1/Smad signaling pathway during the EMT of HMrSV5 cells, indicating its potential therapeutic effect for the control of PF.

scholarly journals The EIF4A3/CASC2/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Junshuang Zhao ◽  
Yang Jiang ◽  
Lian Chen ◽  
Yue Ma ◽  
Haiying Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Feedback Loop ◽  
Biological Effects ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Glioblastoma (GBM) is a common and refractory subtype of high-grade glioma with a poor prognosis. The epithelial-mesenchymal transition (EMT) is an important cause of enhanced glioblastoma invasiveness and tumor recurrence. Our previous study found that retinoic acid receptor-related orphan receptor A (RORA) is a nuclear receptor and plays an important role in inhibiting proliferation and tumorigenesis of glioma. We further confirmed RORA was downregulated in GBM. Thus, we determined whether RORA was involved in the migration, invasion, and EMT of GBM. Human GBM cell lines, U87 and T98G, and patient-derived glioma stem cells (GSCs), GSC2C and GSC4D, were used for in vitro and in vivo experiments. The expressions of RORA, CASC2, and EIF4A3 in GBM cells and GSCs were detected by RT-qPCR and western blotting. The biological effects of RORA, CASC2, and EIF4A3 on GBM migration, invasion, and EMT were evaluated using the migration assay, transwell assay, immunofluorescence staining, and xenograft experiments. We found that RORA inhibited the migration, invasion, and EMT of GBM. CASC2 could bind to, maintain the stability, and promote the nuclear translocation of RORA protein. EIF4A3 could downregulate CASC2 expression via inducing its cleavage, while RORA transcriptionally inhibited EIF4A3 expression, which formed a feedback loop among EIF4A3/CASC2/RORA. Moreover, gene set enrichment analysis (GSEA) and in vitro and in vivo experiments showed RORA inhibited the aggressiveness of GBM by negatively regulating the TGF-β1/Smad signaling pathway. Therefore, The EIF4A3/CASC2/RORA feedback loop regulated TGF-β1/Smad signaling pathway might become a promising therapeutic strategy for GBM treatment.

scholarly journals Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qinlin Shi ◽  
Huan Wu ◽  
Yonglin Li ◽  
Lianju Shen ◽  
Xiaomao Tian ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Wilms Tumor ◽  
Critical Role ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Proliferation And Invasion ◽  
Tgf Β1

Wilms’ tumor (WT) is a common embryonal tumor, and nephrogenic rests play a critical role in WT development. The transforming growth factor β (TGF-β) signaling pathway is fundamental to embryo development and cell growth and proliferation. Moreover, TGF-β contributes to WT development, but the mechanisms of disease pathogenicity are unknown. This study investigated whether the TGF-β signaling pathway was involved in WT and whether blocking TβRI receptor inhibited WT growth, proliferation, and invasion. A total of 60 WT patients with clinical data and surgical specimens were evaluated. Immunohistochemistry (IHC) was used to detect the expression of TGF-β1 and P-smad2/3. In vitro, the proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) protein expression were analyzed using the CCK8 assay, wound healing assay, transwell assay, flow cytometry, and western blot, respectively. In vivo, tumor morphology, tumor size, toxicity, and EMT protein expression were analyzed in tumor-bearing mice treated with a TβRI kinase inhibitor or PBS. High protein levels of TGF-β1 and P-samd2/3 were associated with clinical stage and metastasis or invasion. TβRI inhibition effectively suppressed WT proliferation and migration and promoted apoptosis in the human WT cell line G401, consequently decreasing EMT protein expression. In addition, the TβRI kinase inhibitor significantly impaired the subcutaneous growth of WT. It is worth noting that treatment with the TβRI kinase inhibitor did not cause liver and kidney injury. Our results indicate that the TGF-β/Smad signaling pathway plays a crucial role in WT progression. Blocking the TβRI receptor may be a novel strategy to treat and prevent WT.

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