LncRNA MIR4435-2HG is a potential early diagnostic marker for ovarian carcinoma

2019 ◽  
Vol 51 (9) ◽  
pp. 953-959 ◽  
Author(s):  
Jianming Gong ◽  
Xiaoyang Xu ◽  
Xuanli Zhang ◽  
Yingqiao Zhou
Keyword(s):  
Ovarian Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Cancer Therapies ◽  
Migration Assay ◽  
Invasion And Migration ◽  
And Migration ◽  
Tgf Β1

Abstract LncRNA MIR4435-2HG is characterized as an oncogene in lung cancer. However, its role in ovarian carcinoma (OC) is unclear. In this study, we aimed to investigate the role of MIR4435-2HG in OC. We found that both MIR4435-2HG and transforming growth factor beta 1 (TGF-β1) were upregulated in OC. MIR4435-2HG is associated with tumor metastasis but not with tumor size. Upregulation of MIR4435-2HG distinguished early stage (Stage I and II) OC patients from healthy controls. Correlation analysis showed that plasma levels of MIR4435-2HG and TGF-β1 were positively correlated only in OC patients. qPCR and western blot analysis results showed that MIR4435-2HG overexpression led to upregulation of TGF-β1 in OC cells, while TGF-β1 treatment did not significantly affect MIR4435-2HG expression. Transwell invasion and migration assays showed that MIR4435-2HG and TGF-β1 promoted the invasion and migration of OC cells while TGF-β inhibitor suppressed the invasion and migration of these cells. Further analysis of the Transwell invasion and migration assay results showed that TGF-β inhibitor reduced the effects of MIR4435-2HG overexpression. Therefore, our results suggested that lncRNA MIR4435-2HG may promote OC by upregulating TGF-β1. Further characterization of the functions of MIR4435-2HG in OC may provide novel targets for cancer therapies.

The Role of TGF-β Signaling Regulatory MicroRNAs in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4611-4618 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Majid Khazaei ◽  
Gordon A. Ferns ◽  
Seyed H. Aghaee-Bakhtiari
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Growth Factor Beta ◽  
And Migration ◽  
Multiple Signaling ◽  
Tgf Β1

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high mortality rate. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in normal intestinal tissue function, but has also been implicated in the development of CRC. MicroRNAs (miRNAs) have also recently emerged as important regulators of cancer development and progression. They act by targeting multiple signaling pathways including the TGF-β signaling pathway. There is growing evidence demonstrating that miRNAs target various components of the TGF-β signaling pathway, including TGF-β1, TGF-β2, regulatory SMADs (SMAD1, 2, 3, 5 and 9), co-mediator SMAD4, inhibitory SMADs (SMAD6 and 7) and the TGF-β receptors, and thereby alter the proliferation and migration of CRC cells. In this review, we summarize the data concerning the interaction between TGF-β signaling pathway and miRNAs with the aim to better understanding the CRC molecular mechanisms and hence better management of this disease.

scholarly journals Sos1 Modulates Extracellular Matrix Synthesis, Proliferation, and Migration in Fibroblasts

2021 ◽  
Vol 12 ◽  
Author(s):  
Isabel Fuentes-Calvo ◽  
Carlos Martinez-Salgado
Keyword(s):  
Extracellular Matrix ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Akt Signaling ◽  
Ras Signaling ◽  
Fibroblast Migration ◽  
And Migration ◽  
Tgf Β1 ◽  
Proliferation And Migration

Non-reversible fibrosis is common in various diseases such as chronic renal failure, liver cirrhosis, chronic pancreatitis, pulmonary fibrosis, rheumatoid arthritis and atherosclerosis. Transforming growth factor beta 1 (TGF-β1) is involved in virtually all types of fibrosis. We previously described the involvement of Ras GTPase isoforms in the regulation of TGF-β1-induced fibrosis. The guanine nucleotide exchange factor Son of Sevenless (Sos) is the main Ras activator, but the role of the ubiquitously expressed Sos1 in the development of fibrosis has not been studied. For this purpose, we isolated and cultured Sos1 knock-out (KO) mouse embryonic fibroblasts, the main extracellular matrix proteins (ECM)-producing cells, and we analyzed ECM synthesis, cell proliferation and migration in the absence of Sos1, as well as the role of the main Sos1-Ras effectors, Erk1/2 and Akt, in these processes. The absence of Sos1 increases collagen I expression (through the PI3K-Akt signaling pathway), total collagen proteins, and slightly increases fibronectin expression; Sos1 regulates fibroblast proliferation through both PI3K-Akt and Raf-Erk pathways, and Sos1-PI3K-Akt signaling regulates fibroblast migration. These study shows that Sos1 regulates ECM synthesis and migration (through Ras-PI3K-Akt) and proliferation (through Ras-PI3K-Akt and Ras-Raf-Erk) in fibroblasts, and describe for the first time the role of the Sos1-Ras signaling axis in the regulation of cellular processes involved in the development of fibrosis.

TGF-β1-Induced Long-Term Changes in Neuronal Excitability in Aplysia Sensory Neurons Depend on MAPK

2006 ◽  
Vol 95 (5) ◽  
pp. 3286-3290 ◽  
Author(s):  
Jeannie Chin ◽  
Rong-Yu Liu ◽  
Leonard J. Cleary ◽  
Arnold Eskin ◽  
John H. Byrne
Keyword(s):  
Sensory Neuron ◽  
Transforming Growth Factor Beta ◽  
Neuronal Excitability ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Camp Response Element Binding ◽  
Long Term Changes ◽  
Tgf Β1

Transforming growth factor beta-1 (TGF-β1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-β1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli. Because of the critical role of MAPK in other forms of long-term plasticity in Aplysia, we examined the role of MAPK in TGF-β1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF-β1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-β1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-β1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF-β1-induced long-term changes in neuronal excitability and the phosphorylation of CREB1 were blocked in the presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long-term modulation of sensory neuron function.

scholarly journals Curcumin Treatment Suppresses CCR7 Expression and the Differentiation and Migration of Human Circulating Fibrocytes

2015 ◽  
Vol 35 (2) ◽  
pp. 489-498 ◽  
Author(s):  
Xu-yan Fu ◽  
Dong-wei Zhang ◽  
Ya-dong Li ◽  
Pi-wen Zhao ◽  
Yu-qing Tang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Transforming Growth Factor ◽  
Cell Counting ◽  
Curcumin Treatment ◽  
Healthy Human ◽  
Migration Assay ◽  
Ccr7 Expression ◽  
And Migration ◽  
Tgf Β1 ◽  
Circulating Fibrocytes

Background/Aim: Recent studies have demonstrated that circulating fibrocytes contribute to the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric, has been shown to have anti-fibrotic effects in various organs. We and others have demonstrated that curcumin beneficially affects the development of fibrosis. However the effect of curcumin on circulating fibrocytes has not been reported. Methods: Human circulating fibrocytes were isolated from leukocyte concentrates of healthy human donors and identified based on the expression of CD34, CD45, collagen I (COLI), and chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used to evaluate cell viability. The effect of curcumin on the differentiation and migration of human circulating fibrocytes was evaluated by immunofluorescence staining, flow cytometry and a transwell migration assay. Transforming growth factor (TGF)-β1 secretion was examined by ELISA. Results: Curcumin treatment (72 h; 20 μM) significantly decreased the expression of COL I, α-SMA and CCR7, as well as TGF-βl secretion, in human circulating fibrocytes. The inhibitory effect of curcumin on the differentiation and migration of human circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway, in particular by reducing CCR7 expression. These observed effects may be beneficial in resolving fibrosis by suppressing TGF-β1 secretion. Conclusion: Our results suggest that curcumin has the potential to suppress the differentiation and migration of circulating fibrocytes, which would provide new explanation for curcumin's application in the development of fibrosis in various organs.

scholarly journals The Cell-Permeable Derivative of the Immunoregulatory Metabolite Itaconate, 4-Octyl Itaconate, Is Anti-Fibrotic in Systemic Sclerosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2053
Author(s):  
John Henderson ◽  
Sharadha Dayalan Naidu ◽  
Albena T. Dinkova-Kostova ◽  
Stefan Przyborski ◽  
Richard Stratton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Dermal Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Quinone Oxidoreductase ◽  
Tgf Β1

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that leads to skin fibrosis. Altered metabolism has recently been described in autoimmune diseases and SSc. Itaconate is a product of the Krebs cycle intermediate cis-aconitate and is an immunomodulator. This work examines the role of the cell-permeable derivative of itaconate, 4-octyl itaconate (4-OI), in SSc. SSc and healthy dermal fibroblasts were exposed to 4-OI. The levels of collagen Nrf2-target genes and pro-inflammatory cytokines interleukin 6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) were determined. Levels of reactive oxygen species (ROS) as well as the gene expression of collagen and Cellular Communication Network Factor 2 (CCN2) were measured after transforming growth factor beta 1 (TGF-β1) stimulation in the presence or absence of 4-OI. Wild-type or Nrf2-knockout (Nrf2-KO) mouse embryonic fibroblasts (MEFs) were also treated with 4-OI to determine the role of Nrf2 in 4-OI-mediated effects. 4-OI reduced the levels of collagen in SSc dermal fibroblasts. Incubation with 4-OI led to activation of Nrf2 and its target genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). 4-OI activated antioxidant response element (ARE)-dependent gene expression, reduced inflammatory cytokine release and reduced TGF-β1-induced collagen and ROS production in dermal fibroblasts. The effects of 4-OI are dependent on Nrf2. The cell-permeable derivative of itaconate 4-OI is anti-fibrotic through upregulation of Nrf2 and could be a potential therapeutic option in an intractable disease.

scholarly journals Optimizing Platelet-Rich Plasma (PRP) Injections: A Narrative Review

2020 ◽  
Vol 2 (1) ◽  
pp. e31-e47
Author(s):  
Chris Cherian ◽  
Gerard Malanga ◽  
Ken Mautner
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Vascular Endothelial ◽  
Potential Alternative ◽  
Activating Agent ◽  
Endothelial Growth Factor ◽  
Tgf Β1

Platelet-rich plasma (PRP) is an orthobiologic treatment that has gained popularity as a potential alternative treatment for various musculoskeletal conditions. The physiologic role of platelets in the healing cascade provides clarity regarding its potential as it releases various growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta-1 (TGF-β1), and vascular endothelial growth factor (VEGF). However, there are various characteristics of PRP treatments including platelet count, presence or absence of leukocytes and red blood cells, as well as the use of an activating agent that introduces heterogeneity among preparations. This aim of this article is to provide clarity, where available, regarding the optimal characteristics for PRP treatments regarding tendon and ligament injuries as well as articular and muscular pathology.

Upregulated miR-29c suppresses silica-induced lung fibrosis through the Wnt/β-catenin pathway in mice

2017 ◽  
Vol 37 (9) ◽  
pp. 944-952 ◽  
Author(s):  
X Wang ◽  
K Xu ◽  
XY Yang ◽  
J Liu ◽  
Q Zeng ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Lentiviral Vector ◽  
Lavage Fluid ◽  
Candidate Target ◽  
Tgf Β1

Silicosis is an irreversible lung disease resulting from long-term inhalation of occupational dust containing silicon dioxide. However, the pathogenesis of silicosis has not been clearly understood yet. Accumulating evidence suggests that miR-29 may have a significant anti-fibrotic capacity, meanwhile it may relate to Wnt/β-catenin pathway. The purpose of this study was to discuss the role of miR-29 in the progression of silicosis. A lentiviral vector was constructed, named Lv-miR-29c, which was overexpressing miR-29c. In vivo, intratracheal treatment with Lv-miR-29c significantly increased expression of miR-29c, and reduced expression of β-catenin, matrix metalloproteinase (MMP)-2, and MMP-9 in the lung and levels of transforming growth factor-beta 1 (TGF-β1) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content in silica-administered mice. These results indicated that miR-29c inhibited the development of silica-induced lung fibrosis. Thus, miR-29c may be a candidate target for silicosis treatment via its regulation of the Wnt/β-catenin pathway.

scholarly journals Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Demin Cheng ◽  
Qi Xu ◽  
Yue Wang ◽  
Guanru Li ◽  
Wenqing Sun ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Lung Epithelial Cells ◽  
Lung Fibroblasts ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. Methods The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. Conclusions In this study, we identified that metformin might be a potential drug for silicosis treatment.

Sign in / Sign up

Export Citation Format

Share Document