TGF-β induced miR-132 enhances the activation of TGF-β signaling through inhibiting SMAD7 expression in glioma cells

Wang, Zhaohui; Zhang, Qi-Shun; Duan, Yan-Li; Zhang, Jianlei; Li, Guo-Fei; Zheng, Dong-Lin

doi:10.1016/j.bbrc.2015.05.001

Cited by 28 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Strikingly, Smad7 can block TGF-β signaling through various means[80-82], such as binding TGFβRI to inhibit the interaction-dependent activation of Smad2, collaborating with other effectors to induce TGFβRI degradation, and regulating the Wnt/β-catenin pathway to influence TGF-β-induced apoptosis[83]. Similarly, targeting of Smad7 enhances TGF-β pathway activation[84]. …”

Section: Novel Therapeutic Targets In Liver Fibrosismentioning

confidence: 99%

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Zhang¹,

Yuan²,

He³

et al. 2016

WJG

466

327

View full text Add to dashboard Cite

Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.

show abstract

Section: Novel Therapeutic Targets In Liver Fibrosismentioning

confidence: 99%

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Zhang¹,

Yuan²,

He³

et al. 2016

WJG

466

327

View full text Add to dashboard Cite

show abstract

“…TGF-β may upregulate the miR-132 expression level in dose-and time-dependent manners, and may further enhance the activation of TGF-β signaling by inhibiting SMAD7 expression in glioma cells (18). TGF-β additionally serves important regulatory functions in CC, as for example, the oncoproteins of HPVs may stimulate TGF-β1 expression in CC cells, which in turn suppresses the host immune surveillance towards CC, and triggers the EMT process, migration and metastasis of CC cells (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

“…Transforming growth factor (TGF)-β is a multifunctional cytokine and may induce numerous important signaling pathways in several types of cancer cells (15,16). Furthermore, TGF-β may regulate the expression of TSLP in the intervertebral disc tissue (17) and regulate the expression of miR-132 in glioma cells (18). However, it remains unknown whether TSLP regulates the biological behaviors by modulating the expression of miR-132 in CC.…”

Section: Introductionmentioning

confidence: 99%

Human thymic stromal lymphopoietin promotes the proliferation and invasion of cervical cancer cells by downregulating microRNA‑132 expression

et al. 2017

View full text Add to dashboard Cite

Abstract. Thymic stromal lymphopoietin (TSLP), produced by cervical cancer (CC) cells, promotes angiogenesis, and the recruitment and functional regulation of eosinophils. It has been reported that microRNA (miR)-132 is aberrantly decreased in CC tissues. However, the function and mechanism of TSLP on the biological behaviors of CC cells is largely unknown. The aim of the present study was to investigate the effect of TSLP on the expression of miR-132 and the proliferation and invasion in vitro of CC cell lines, namely, HeLa and SiHa cells. The transcrpitional level of miR-132 was analyzed using reverse transcription-quantitative polymerase chaon reaction. The proliferation, invasion, and the expression of proliferation and invasion-related molecules in HeLa and SiHa cells in vitro were evaluated using bromodeoxyuridine cell proliferation, Matrigel invasion assays, flow cytometry and ELISA, respectively. Here, it was revealed that recombinant human TSLP (rhTSLP) downregulated the expression levels of miR-132 in HeLa and SiHa cells, and by contrast, the neutralizing antibodies for TSLP or TSLP receptor (TSLPR) upregulated miR-132 expression levels in HeLa and SiHa cells. The overexpression of miR-132 resulted in a lowered proliferation and invasiveness, decreased levels of proliferation-associated molecules marker of proliferation Ki-67 and proliferating cell nuclear antigen, and the decreased production of matrix metalloproteinase (MMP)2 and MMP9 in HeLa and SiHa cells. Compared with the control group, there was a higher level of proliferation and invasion in HeLa and SiHa cells following stimulation with rhTSLP. However, these effects induced by rhTSLP were significantly impaired in HeLa and SiHa cells with miR-132 overexpression. The results of the present study indicated that TSLP produced by CC cells downregulated miR-132 expression, and stimulated the proliferation and invasion of CC cells, thereby further promoting the development of CC. IntroductionCervical cancer (CC) is one of the most common gynecological malignancies with high rates of morbidity (0.001-0.05%) and mortality (0.0024-0.0175%), endangering the health and quality of life of women globally (1). Although the decreased incidence of CC has primarily been attributed to the widespread use of cytological screening, invasive CC remains an issue regarding the mortality rates of patients with CC. Thus, the elucidation of the molecular pathogenesis of CC is urgently required. The pathogenesis of CC remains enigmatic and may be connected with numerous factors, including infection with high-risk human papillomaviruses (HPVs) (2).Thymic stromal lymphopoietin (TSLP) is primarily produced by stromal cells, epithelial cells, fibroblasts, keratinocytes, basophils and other types of cells, including mast cells, smooth muscle cells, fibroblasts, dendritic cells, trophoblasts, and cancer or cancer-associated cells (3-5). TSLP may trigger helper T-cell 2 cytokines, and is associated with airway inflammatory disease, immunoglobulin E production, allergic respons...

show abstract

“…Functionally, miR-132 promoted lymphangiogenic response, whereas miR-132 inhibition suppressed LECs proliferation, migration and tube formation. TGF-β plays an important role in lymphangiogenesis [33,34], and the correlation of miR-132 with TGF-β/Smad signaling was revealed in several cancer [35,37]. We thus investigated whether miR-132 promoted lymphangiogenic response by regulating TGF-β/Smad signaling.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

“…Additionally, the correlation of miR-132 with TGF-β/Smad signaling was revealed in several cancer, including glioma [35], prostate cancer [36] and non-small cell lung cancer [37]. Therefore, we next investigated whether miR-132 promotes lymphangiogenic response by regulating TGF-β/Smad signaling.…”

Section: Exosomes From-adscs/vegf-c (Exosome-adscs/ Vegf-c) Promote Lmentioning

confidence: 99%

Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway

Wang

Cao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Lymphangiogenesis plays an important role in the pathogenesis of inflammatory bowel diseases (IBD), and vascular endothelial growth factor-C (VEGF-C) is a powerful lymphangiogenic factor. Adipose-derived stem cells (ADSCs) are a promising therapeutic modality for several diseases because ADSCs secret growth factors and exosomes, which modulate hostile microenvironments affected by diseases. However, the effect of exosomes on VEGF-C-dependent lymphangiogenesis and its mechanism remain unclear. Methods: ADSCs were cultured in media with or without recombinant VEGF-C and exosomes were extracted from conditioned medium (CM). Lymphatic endothelial cells (LECs) were treated with ADSCs-derived exosomes, then proliferation, migration and tube formation of LECs were assayed using cell counting Kit-8 (CCK-8), transwell chamber inserts and matrigel-based tube formation assay respectively. Results: We identified significantly higher levels of miR-132 in exosomes isolated from VEGF-C-treated ADSCs (ADSCs/VEGF-C) than in those from ADSCs control. miR-132 was directly transferred from ADSCs to the LECs by the mediation of exosomes. The exosomes from ADSCs/VEGF-C promoted LECs proliferation, migration, and tube formation more potently than the exosomes from ADSCs, whereas pretreatment of ADSCs with miR-132 inhibitor attenuates VEGF-C-dependent lymphangiogenic response. Finally we reveal that miR-132 promotes lymphangiogenic response by directly targeting Smad-7 and regulating TGF-β/Smad signaling. Conclusion: These data provide new insights into the role of ADSCs-derived exosomes as an important player in VEGF-C-dependent lymphangiogenesis.

show abstract

TGF-β induced miR-132 enhances the activation of TGF-β signaling through inhibiting SMAD7 expression in glioma cells

Cited by 28 publications

References 22 publications

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Human thymic stromal lymphopoietin promotes the proliferation and invasion of cervical cancer cells by downregulating microRNA‑132 expression

Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway

Contact Info

Product

Resources

About