scholarly journals TGF-β2-induced NEAT1 regulates lens epithelial cell proliferation, migration and EMT by the miR-26a-5p/FANCE axis

2021 ◽  
Vol 14 (11) ◽  
pp. 1674-1682
Author(s):  
Xiao-Hui Yu ◽  
◽  
Cheng-Fang Li ◽  
Keyword(s):  
Cell Cycle ◽  
Transforming Growth Factor Beta ◽  
Cell Cycle Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Complementation Group ◽  
Lens Epithelial Cell ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
And Migration

AIM: To explore the regulatory mechanism of nuclear paraspeckle assembly transcript 1 (NEAT1) in the pathogenesis of posterior capsule opacification (PCO). METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was executed to analyze NEAT1 and microRNA (miR)-26a-5p expression in transforming growth factor-beta 2 (TGF-β2)-disposed lens epithelial cells (LECs). The proliferation, cell cycle progression, apoptosis, and migration of TGF-β2-disposed LECs were evaluated. The relationship between NEAT1 or fanconi anemia (FA) complementation group E (FANCE) and miR-26a-5p was verified by dual-luciferase reporter assay. RESULTS: TGF-β2 induced NEAT1 expression in LECs. NEAT1 inhibition accelerated apoptosis, cell cycle arrest, decreased proliferation, epithelial-mesenchymal transition (EMT), and migration of TGF-β2-disposed LECs. NEAT1 sponged miR-26a-5p to further regulate FANCE expression. Rescue experiments presented that miR-26a-5p downregulation overturned NEAT1 silencing-mediated impacts on TGF-β2-disposed LEC biological behaviors. Additionally, FANCE overexpression reversed miR-26a-5p mimic-mediated impacts on TGF-β2-disposed LEC biological behaviors. CONCLUSION: TGF-β2-induced NEAT1 facilitates LEC proliferation, migration, and EMT by upregulating FANCE via sequestering miR-26a-5p.

scholarly journals miR-4458 inhibits the epithelial–mesenchymal transition of hepatocellular carcinoma cells by suppressing the TGF-β signaling pathway via targeting TGFBR1

2020 ◽  
Vol 52 (5) ◽  
pp. 554-562
Author(s):  
Yuke Zhang ◽  
Kun Shi ◽  
Hang Liu ◽  
Wei Chen ◽  
Yunhai Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Mesenchymal Transition ◽  
Gene Assay ◽  
Hcc Cells

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. MicroRNAs play a pivotal role in the progression of various cancers. To date, very little attention has been paid to miR-4458. Therefore, the aim of our study was to explore the function and underlying molecular mechanism of miR-4458 in HCC. We found that the expression of miR-4458 was reduced in HCC tissues and cell lines. Forced overexpression of miR-4458 inhibited the migration, invasion, and epithelial–mesenchymal transition (EMT) of HCC cells, while downregulation of miR-4458 promoted the aggressive phenotype. Furthermore, transforming growth factor beta receptor 1 (TGFBR1), the modulator of the TGF-β signaling pathway, was verified to be a novel target gene of miR-4458 by dual-luciferase reporter gene assay. Upregulated miR-4458 dramatically abolished TGFBR1 and p-Smad2/3 expression, thus blocking the TGF-β signaling pathway. Moreover, restoration of TGFBR1 partially rescued the miR-4458-mediated suppressive effect on the migration, invasion, and EMT and reactivated the TGF-β signaling pathway in HCC cells. In summary, our findings first demonstrated a mechanism of miR-4458 in HCC cell migration, invasion, and EMT by regulating the TGF-β signaling pathway via directly targeting TGFBR1.

scholarly journals RASSF10 Is a TGFβ-Target That Regulates ASPP2 and E-Cadherin Expression and Acts as Tumor Suppressor That Is Epigenetically Downregulated in Advanced Cancer

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1976 ◽  
Author(s):  
Antje M. Richter ◽  
Miriam M. Küster ◽  
Michelle L. Woods ◽  
Sara K. Walesch ◽  
Mira Y. Gökyildirim ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Transforming Growth Factor Beta ◽  
Cell Cycle Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Human Cancers ◽  
Tumor Suppressive Function ◽  
E Cadherin

The Ras Association Domain Family (RASSF) encodes members of tumor suppressor genes which are frequently inactivated in human cancers. Here, the function and the regulation of RASSF10, that contains a RA (Ras-association) and two coiled domains, was investigated. We utilized mass spectrometry and immuno-precipitation to identify interaction partners of RASSF10. Additionally, we analyzed the up- and downstream pathways of RASSF10 that are involved in its tumor suppressive function. We report that RASSF10 binds ASPP1 (Apoptosis-stimulating protein of p53) and ASPP2 through its coiled-coils. Induction of RASSF10 leads to increased protein levels of ASPP2 and acts negatively on cell cycle progression. Interestingly, we found that RASSF10 is a target of the EMT (epithelial mesenchymal transition) driver TGFβ (Transforming growth factor beta) and that negatively associated genes of RASSF10 are significantly over-represented in an EMT gene set collection. We observed a positive correlation of RASSF10 expression and E-cadherin that prevents EMT. Depletion of RASSF10 by CRISPR/Cas9 technology induces the ability of lung cancer cells to proliferate and to invade an extracellular matrix after TGFβ treatment. Additionally, knockdown of RASSF10 or ASPP2 induced constitutive phosphorylation of SMAD2 (Smad family member 2). Moreover, we found that epigenetic reduction of RASSF10 levels correlates with tumor progression and poor survival in human cancers. Our study indicates that RASSF10 acts a TGFβ target gene and negatively regulates cell growth and invasion through ASPP2. This data suggests that epigenetic loss of RASSF10 contributes to tumorigenesis by promoting EMT induced by TGFβ.

scholarly journals Inhibition of TGF-β/Smad3 Signaling Disrupts Cardiomyocyte Cell Cycle Progression and Epithelial–Mesenchymal Transition-Like Response During Ventricle Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanyuan Peng ◽  
Wenyuan Wang ◽  
Yunzheng Fang ◽  
Haichen Hu ◽  
Nannan Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cardiac Regeneration ◽  
Cycle Progression ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Proliferation And Migration

Unlike mammals, zebrafish can regenerate injured hearts even in the adult stage. Cardiac regeneration requires the coordination of cardiomyocyte (CM) proliferation and migration. The TGF-β/Smad3 signaling pathway has been implicated in cardiac regeneration, but the molecular mechanisms by which this pathway regulates CM proliferation and migration have not been fully illustrated. Here, we investigated the function of TGF-β/Smad3 signaling in a zebrafish model of ventricular ablation. Multiple components of this pathway were upregulated/activated after injury. Utilizing a specific inhibitor of Smad3, we detected an increased ratio of unrecovered hearts. Transcriptomic analysis suggested that the TGF-β/Smad3 signaling pathway could affect CM proliferation and migration. Further analysis demonstrated that the CM cell cycle was disrupted and the epithelial–mesenchymal transition (EMT)-like response was impaired, which limited cardiac regeneration. Altogether, our study reveals an important function of TGF-β/Smad3 signaling in CM cell cycle progression and EMT process during zebrafish ventricle regeneration.

scholarly journals miRNA-26b suppresses the TGF-β2-induced progression of HLE-B3 cells via the PI3K/Akt pathway

2021 ◽  
Vol 14 (9) ◽  
pp. 1350-1358
Author(s):  
En Shi ◽  
◽  
Liu-Yi Xie ◽  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Lens Epithelial Cell ◽  
Human Lens ◽  
Posterior Capsular Opacification ◽  
Akt Pathway ◽  
Epithelial Cell Line ◽  
Mesenchymal Transition ◽  
Human Lens Epithelial Cell

AIM: To study the effect of miR-26b on lens epithelial cells induced by transforming growth factor beta (TGF-β) 2 and the underlying signaling pathways. METHODS: Human lens epithelial cell line B-3 (HLE-B3) was incubated with TGF-β2 (5 ng/mL) and then transfected with miR-26b mimics. The expression of miR-26b was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), while 5’-bromodeoxyuridine (BrdU) and wound-healing assays were used to measure the growth and migration of HLE-B3 cells, respectively. The expression of epithelial-mesenchymal transition (EMT) markers and the activity of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway were measured by Western blotting assay and immunofluorescence staining. Electron microscopy was also used to observe cellular morphology. RESULTS: The expression levels of miR-26b were significantly reduced in human posterior capsular opacification-attached lens tissue and TGF-β2-stimulated HLE-B3 cells. In the presence of TGF-β2, the growth, migration, and EMT of HLE-B3 cells were distinctly enhanced; these effects were attenuated by the administration of miR-26b mimics. Furthermore, the overexpression of miR-26b significantly reduced upregulation of the PI3K/Akt pathway when stimulated by TGF-β2 in HLE-B3 cells. Moreover, the addition of an activator (740 Y-P) led to the upregulation of the PI3K/Akt pathway and abolished the protective effect of miR-26b on the HLE-B3 cells that was mediated by TGF-β2. CONCLUSION: The miR-26b suppresses TGF-β2-induced growth, migration, and EMT in HLE-B3 cells by regulating the PI3K/Akt signaling pathway.

scholarly journals Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 348 ◽  
Author(s):  
Ravindran ◽  
Pasha ◽  
Agouni ◽  
Munusamy
Keyword(s):  
Er Stress ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Cell Injury ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Mesenchymal Transition

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN.

scholarly journals Tumor-Suppressive Function of lncRNA-MEG3 in Glioma Cells by Regulating miR-6088/SMARCB1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Gong ◽  
Meng-Yi Huang
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Favorable Effect ◽  
Mesenchymal Transition ◽  
Gene Assay ◽  
And Migration ◽  
Proliferation And Migration ◽  
Glioma Progression

Objective. Mounting evidence has elaborated the implication of long noncoding RNAs (lncRNAs) in tumorigenesis of several cancers, including glioma. However, little was known about the mechanism of lncRNA maternally expressed gene 3 (MEG3) in the development and progression of glioma. This work is designed to explore the effect of MEG3 on glioma progression and its possible mechanism. Methods. Expressions of lncRNA-MEG3 and SMARCB1 were detected in human glioblastoma U87 and U251 cell lines. Gain and loss of function of MEG3 or/and miR-6088 was performed in U87 and U251 cells to observe its effect on cell proliferation and migration as well as on epithelial-mesenchymal transition (EMT) related markers. Luciferase reporter gene assay was employed to inspect the interactions among MEG3, miR-6088, and SMARCB1. Results. MEG3 and SMARCB1 expressions were downregulated in glioma cells. Transfection of pcDNA3.1-MEG3 or pcDNA3.1-SMARCB1 plasmids could clearly block cell proliferation, migration, and EMT progression. MEG3 functions as a sponge for miR-6088, while SMARCB1 is a downstream protein of miR-6088. Transfection of miR-6088 mimic or si-SMARCB1 could obviously reverse the favorable effect of pcDNA3.1-MEG3 on glioma progression. Conclusion. Collectively, the evidence in this study indicated that MEG3 was downregulated in glioma cells and inhibited proliferation and migration of glioma cells via regulating miR-6088/SMARCB1 axis.

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