LncRNA NEAT1 promotes proliferation, migration, invasion and epithelial-mesenchymal transition process in TGF-β2-stimulated lens epithelial cells through regulating the miR-486-5p/SMAD4 axis

Abstract Background Abnormal proliferation, metastasis and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) are direct factors of posterior capsular opacification (PCO). Nuclear enriched abundant transcript 1 (NEAT1) has been shown to promote cell proliferation, metastasis and EMT, but whether it affects the progression of PCO is unclear. Methods The expression of NEAT1, microRNA-486-5p (miR-486-5p) and Drosophila mothers against decapentaplegic 4 (SMAD4) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of cells was measured via 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was employed to detect the migration and invasion of cells. The levels of EMT marker proteins, SMAD4 protein and transforming growth factor-β (TGF-β)/SMAD signaling pathway-related proteins were assessed by western blot (WB) analysis. Further, the relationship between miR-486-5p and NEAT1 or SMAD4 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and biotin-labeled RNA pull-down assay. Results NEAT1 is upregulated and miR-486-5p is downregulated in the posterior capsular tissues of PCO patients and TGF-β2-induced LECs. Interference of NEAT1 reverses the promoting effect of TGF-β2 on the proliferation, migration, invasion and EMT of LECs. MiR-486-5p can be sponged by NEAT1, and its inhibitor reverses the suppression effect of NEAT1 silencing on the progression of TGF-β2-induced LECs. SMAD4 functions as a target of miR-486-5p, and its overexpression recovers the inhibition effect of miR-486-5p overexpression on the progression of TGF-β2-induced LECs. The activity of the TGF-β/SMAD signaling pathway is regulated by the NEAT1/miR-486-5p/SMAD4 axis. Conclusion Our study shows that NEAT1 has a positive effect on the progression of PCO and is expected to become a new target for PCO treatment.

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IGF-1 Promotes Epithelial-Mesenchymal Transition of Lens Epithelial Cells That is Conferred by miR-3666 Loss

10.21203/rs.3.rs-488224/v1 ◽

2021 ◽

Author(s):

Zhan Shi ◽

Xiumei Zhao ◽

Ying Su ◽

Chao Wang ◽

Hongyan Ge ◽

...

Keyword(s):

Epithelial Cells ◽

Vision Loss ◽

Epithelial Mesenchymal Transition ◽

Luciferase Reporter ◽

Posterior Capsular Opacification ◽

Lens Epithelial Cells ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Mesenchymal Transformation ◽

New Strategies

Abstract The abnormal proliferation, migration and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) are the main reasons of vision loss caused by posterior capsular opacification (PCO) after cataract surgery. Insulin-like growth factor-1 (IGF-1) was found to be associated with the pathogenesis of cataract, but its biological role in PCO is poorly understood. In the present study, IGF-1 overexpression facilitated the proliferation, migration and EMT, whereas knockdown of IGF-1 markedly suppressed the proliferation, migration and TGF-β2-induced EMT of LECs. Additionally, To evaluate valuable microRNAs (miRNAs) which target IGF-1 to modulate LECs-EMT, we predicted miR-3666 might regulate IGF-1 by binding its 3’UTR according bioinformatics database. Furthermore, we verified that miR-3666 directly targeted to IGF-1 by luciferase reporter assay. By using miR-3666 mimics, cells proliferation, migration, and invasion were suppressed, while were enhanced by reduction of miR-3666. Knockout of IGF1 reverses the effect of miR-3666 inhibitor on the malignant behavior of LECs. These results indicate the role for miR-3666/IGF-1 in LECs-EMT that offer new strategies for the therapy and prevention of PCO.

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The Overexpression of Keratin 23 Promotes Migration of Ovarian Cancer via Epithelial-Mesenchymal Transition

BioMed Research International ◽

10.1155/2020/8218735 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Meng Ren ◽

Yan Gao ◽

Qi Chen ◽

Hongyu Zhao ◽

Xiaoting Zhao ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Migration ◽

Signaling Pathway ◽

Cell Lines ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Cell Migration And Invasion ◽

Smad Signaling ◽

Smad Signaling Pathway

Background. Keratin 23 (KRT23) is a new member of the KRT gene family and known to be involved in the development and migration of various types of tumors. However, the role of KRT23 in ovarian cancer (OC) remains unclear. This study is aimed at investigating the function of KRT23 in OC. Methods. The expression of KRT23 in normal ovarian and OC tissues was determined using the Oncomine database and immunohistochemical staining. Reverse transcription quantitative polymerase chain reaction assay was used to analyze the expression of KRT23 in normal ovarian epithelial cell lines and OC cell lines. Small interfering RNA (siRNA), wound healing assay, and transwell assay were conducted to detect the effects of KRT23 on OC cell migration and invasion. Further mechanistic studies were verified by the Gene Expression Profiling Interactive Analysis platform, Western blotting, and immunofluorescence staining. Results. KRT23 was highly expressed in OC tissues and cell lines. High KRT23 expression could regulate OC cell migration and invasion, and the reduction of KRT23 by siRNA inhibited the migration and invasion of OC cells in vitro. Furthermore, KRT23 mediated epithelial-mesenchymal transition (EMT) by regulating p-Smad2/3 levels in the TGF-β/Smad signaling pathway. Conclusions. These results demonstrate that KRT23 plays an important role in OC migration via EMT by regulating the TGF-β/Smad signaling pathway.

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Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway

Journal of Cancer ◽

10.7150/jca.30359 ◽

2019 ◽

Vol 10 (16) ◽

pp. 3778-3788 ◽

Cited By ~ 4

Author(s):

Jie Ning ◽

Xinqi Ma ◽

Chongde Long ◽

Yuxiang Mao ◽

Xielan Kuang ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Lens Epithelial Cells ◽

Smad Signaling ◽

Smad Signaling Pathway

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

SSRN Electronic Journal ◽

10.2139/ssrn.3714633 ◽

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

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Transforming growth factor-β2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of RAGE

Biochemical Journal ◽

10.1042/bcj20210069 ◽

2021 ◽

Vol 478 (12) ◽

pp. 2285-2296

Author(s):

Mi-Hyun Nam ◽

Mina B. Pantcheva ◽

Johanna Rankenberg ◽

Ram H. Nagaraj

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Knockout Mice ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Lens Epithelial Cells ◽

Wild Type ◽

Mesenchymal Transition ◽

Smad Signaling ◽

Transforming Growth Factor Β2

Transforming growth factor-β2 (TGFβ2)-mediated epithelial to mesenchymal transition (EMT) in lens epithelial cells (LECs) has been implicated in fibrosis associated with secondary cataracts. In this study, we investigated whether the receptor for advanced glycation end products (RAGE) plays a role in TGFβ2-mediated EMT in LECs. Unlike in the LECs from wild-type mice, TGFβ2 failed to elicit an EMT response in LECs from RAGE knockout mice. The lack of RAGE also diminished TGFβ2-mediated Smad signaling. In addition, treatment with TGFβ2 increased IL-6 levels in LECs from wild-type mice but not in those from RAGE knockout mice. Treatment of human LECs with the RAGE inhibitor FPS-ZM1 reduced TGFβ2-mediated Smad signaling and the EMT response. Unlike that in wild-type lenses, the removal of fiber cell tissue in RAGE knockout lenses did not result in elevated levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and integrin β1 in capsule-adherent LECs. Taken together, these results suggest that TGFβ2 signaling is intricately linked to RAGE. Targeting RAGE could be explored as a therapeutic strategy against secondary cataracts.

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Lens epithelial cells-induced pluripotent stem cells as a model to study epithelial-mesenchymal transition during posterior capsular opacification

Biochemistry and Biophysics Reports ◽

10.1016/j.bbrep.2019.100696 ◽

2019 ◽

Vol 20 ◽

pp. 100696

Author(s):

Roy Joseph ◽

Katie Bales ◽

Kiran Srivastava ◽

Om Srivastava

Keyword(s):

Stem Cells ◽

Epithelial Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Epithelial Mesenchymal Transition ◽

Posterior Capsular Opacification ◽

Lens Epithelial Cells ◽

Mesenchymal Transition ◽

Induced Pluripotent

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Involvement of Ras GTPase-activating protein SH3 domain-binding protein 1 in the epithelial-to-mesenchymal transition-induced metastasis of breast cancer cells via the Smad signaling pathway

Oncotarget ◽

10.18632/oncotarget.3636 ◽

2015 ◽

Vol 6 (19) ◽

pp. 17039-17053 ◽

Cited By ~ 18

Author(s):

Hao Zhang ◽

Yan Ma ◽

Shenghua Zhang ◽

Hong Liu ◽

Hongwei He ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Gtpase Activating Protein ◽

Mesenchymal Transition ◽

Smad Signaling ◽

Ras Gtpase ◽

Smad Signaling Pathway

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/1479136 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

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.

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