TGF-β1 Downregulates COX-2 Expression Leading to Decrease of PGE2 Production in Human Lung Cancer A549 Cells, Which Is Involved in Fibrotic Response to TGF-β1

Takai, Erina; Tsukimoto, Mitsutoshi; Kojima, Shuji

doi:10.1371/journal.pone.0076346

Cited by 55 publications

(44 citation statements)

References 52 publications

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“…Many critical steps in intracellular TGF-β signaling are mediated by Smad proteins. However, Smad-independent signaling transduction pathways are also involved in the biological activities of TGF-β [13,14]. As the Smad pathway principally regulates gene expression, it was originally thought that nonSmad effectors mediate the rapid or direct effects of TGF-β on tumor invasiveness.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: TGF-β Regulates Survivin to Affect Cell Cycle and the Expression of EGFR and MMP9 in Glioblastoma

et al. 2015

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Transforming growth factor beta (TGF-β) is suggestive of a molecular target for cancer therapy due to its involvement in cell cycle, differentiation, and morphogenesis. Meanwhile, survivin is identified as an apoptosis inhibitor and involved in tumorgenesis. Here, we aimed to investigate the potential associations between TGF-β and survivin in glioblastoma U87 cell line. Survivin small interfering RNA (siRNA), Western blotting, and cell cycle analysis were introduced to detect relevant proteins in TGF-β pathways. In this study, we observed a concentration- and time-dependent increase of survivin expression after treatment with TGF-β1. However, the kinase inhibitors U0126 and LY294002 inhibited the upregulation of survivin in comparison with DMSO. In addition, survivin siRNA effectively abrogated survivin expression in U87 cells, therefore affected cells' entry into the S phase of cell cycle, and then repressed the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9) in comparison with non-transfection. In conclusion, the present study shows that TGF-β upregulates survivin expression via ERK and PI3K/AKT pathway, leading to glioblastoma cell cycle progression. Thus, the blockade of survivin will allow for the treatment of glioblastoma, partially attributing to the inhibition of EGFR and MMP9 expression.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: TGF-β Regulates Survivin to Affect Cell Cycle and the Expression of EGFR and MMP9 in Glioblastoma

et al. 2015

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“…8). TGF-␤ has previously been characterized to have dual effects on COX-2 (24,36,45,51,56). A study in human nonsmall cell lung cancer A549 cells showed that TGF-␤ was able to downregulate COX-2 (56).…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-β induces microRNA-29b to promote murine alveolar macrophage dysfunction after bone marrow transplantation

Domingo-Gonzalez

Wilke

Laouar

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Moore BB. Transforming growth factor-␤ induces microRNA-29b to promote murine alveolar macrophage dysfunction after bone marrow transplantation. Am J Physiol Lung Cell Mol Physiol 308: L86 -L95, 2015. First published October 31, 2014 doi:10.1152/ajplung.00283.2014.-Hematopoietic stem cell transplantation (HSCT) is complicated by pulmonary infections that manifest posttransplantation. Despite engraftment, susceptibility to infections persists long after reconstitution. Previous work using a murine bone marrow transplant (BMT) model implicated increased cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in promoting impaired alveolar macrophage (AM) responses. However, mechanisms driving COX-2 overexpression remained elusive. Previously, transforming growth factor-␤ (TGF-␤) signaling after BMT was shown to promote hypomethylation of the COX-2 gene. Here, we provide mechanistic insight into how this occurs and show that TGF-␤ induces microRNA (miR)-29b while decreasing DNA methyltransferases (DNMT)1, DNMT3a, and DNMT3b in AMs after BMT. De novo DNMT3a and DNMT3b were decreased upon transient transfection of miR-29b, resulting in decreased methylation of the COX-2 promoter and induction of COX-2. As a consequence, miR-29b-driven upregulation of COX-2 promoted AM dysfunction, and transfection of BMT AMs with a miR-29b inhibitor rescued the bacterialkilling defect. MiR-29b-mediated defects in BMT AMs were dependent on increased levels of PGE2, as miR-29b-transfected AMs treated with a novel E prostanoid receptor 2 antagonist abrogated the impaired bacterial killing. We also demonstrate that patients that have undergone HSCT exhibit increased miR-29b; thus these studies highlight miR-29b in driving defective AM responses and identify this miRNA as a potential therapeutic target. alveolar macrophage; bone marrow transplantation; microRNA-29b; prostaglandin; transforming growth factor-␤

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“…VEGF increases the secretion of various proteases and matrix degradation enzymes in tumors, further contributing to tumor invasion and metastasis [36]. TGF-β1 is a multifunctional cytokine that regulates various physiological processes such as cell growth, differentiation, immune suppression, extracellular matrix deposition, and tumorigenesis [37][38][39]. Several studies demonstrated that TGF-β1 promotes tumor metastasis, angiogenesis, and escape from immune surveillance and is secreted in several cancers such as breast and lung cancers [38,[40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Platelet VEGF and serum TGF-β1 levels predict chemotherapy response in non-small cell lung cancer patients

Wei

et al. 2015

Tumor Biol.

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We examined the levels of platelet vascular endothelial growth factor (VEGF(PLT)) and serum level of transforming growth factor beta 1 (TGF-β1) in non-small cell lung cancer (NSCLC) patients before and after chemotherapy to assess their clinical value as biomarkers. A total of 115 subjects were recruited at the First Hospital of Qinhuangdao between July 2012 and October 2013, including 65 NSCLC patients receiving chemotherapy (NSCLC group) and 50 healthy controls (control group). All NSCLC patients received gemcitabine plus cisplatin (GP regimen) for a total of two courses. VEGF(PLT) and serum TGF-β1 levels were measured before and after chemotherapy using enzyme-linked immunosorbent assay (ELISA). Platelet count was obtained using the Abbott CD-1600 auto blood analyzer. NSCLC group was categorized into complete response (CR) plus partial response (PR) group and stable disease (SD) plus progressive disease (PD) group based on the results of CT scans obtained 1 week after chemotherapy. Our results revealed that VEGF(PLT) and serum TGF-β1 levels were significantly higher in NSCLC group before chemotherapy, compared to the control group (VEGF(PLT), 0.813 ± 0.072 vs. 0.547 ± 0.024; t = 26.48; P < 0.001 and TGF-β1, 46.00 ± 4.47 vs. 16.43 ± 2.12; t = 44.87; P < 0.001). Importantly, VEGF(PLT) and serum TGF-β1 levels decreased significantly after chemotherapy in CR + PR group in comparison with before chemotherapy (VEGF(PLT), 0.453 ± 0.078 vs. 0.814 ± 0.127; t = 15.51; P < 0.001 and TGF-β1, 20.17 ± 2.43 vs. 42.13 ± 4.54; t = 27.31; P < 0.001). By contrast, VEGF(PLT) and serum TGF-β1 levels were markedly higher after chemotherapy in the SD + PD group in comparison with before chemotherapy (VEGF(PLT), 0.816 ± 0.043 vs. 1.065 ± 0.016; t = 22.38; P < 0.001 and TGF-β1, 41.80 ± 5.46 vs. 45.83 ± 4.62; t = 2.32; P = 0. 03). Our results show that NSCLC patients exhibit high VEGF(PLT) and serum TGF-β1 levels, and VEGF(PLT) and TGF-β1 levels correlate with chemotherapy response to GP regimen. Therefore, VEGF(PLT) and serum TGF-β1 levels are valuable biomarkers in clinical monitoring of NSCLC patients.

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TGF-β1 Downregulates COX-2 Expression Leading to Decrease of PGE2 Production in Human Lung Cancer A549 Cells, Which Is Involved in Fibrotic Response to TGF-β1

Cited by 55 publications

References 52 publications

RETRACTED ARTICLE: TGF-β Regulates Survivin to Affect Cell Cycle and the Expression of EGFR and MMP9 in Glioblastoma

RETRACTED ARTICLE: TGF-β Regulates Survivin to Affect Cell Cycle and the Expression of EGFR and MMP9 in Glioblastoma

Transforming growth factor-β induces microRNA-29b to promote murine alveolar macrophage dysfunction after bone marrow transplantation

Platelet VEGF and serum TGF-β1 levels predict chemotherapy response in non-small cell lung cancer patients

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