scholarly journals PPARα Regulates the Proliferation of Human Glioma Cells through miR-214 and E2F2

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yong Gao ◽  
Dongfeng Han ◽  
Laisheng Sun ◽  
Qihua Huang ◽  
Guangchao Gai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Nuclear Hormone Receptor ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anaplastic Gliomas ◽  
Glioma Cell Proliferation

Peroxisome proliferator-activated receptor α (PPARα) is a member of the nuclear hormone receptor superfamily and functions as a transcription factor. Previous work showed that PPARα plays multiple roles in lipid metabolism in tissues such as cardiac and skeletal muscle, liver, and adipose tissue. Recent studies have discovered additional roles for PPARα in cell proliferation and metabolism, as well as tumor progression. PPARα is aberrantly expressed in various cancers, and activated PPARα inhibits the proliferation of some tumor cells. However, there have been no studies of PPARα in human gliomas. Here, we show that PPARα is expressed at lower levels in anaplastic gliomas and glioblastoma multiforme (GBM) tissue compared with low-grade gliomas tissue, and low expression is associated with poor patient prognosis. PPARα activates transcription of dynamin-3 opposite strand (DNMO3os), which encodes a cluster of miR-214, miR-199a-3p, and miR-199a-5p microRNAs. Of these, miR-214 is transcribed at particularly high levels. PPARα-induced miR-214 expression causes downregulation of its target E2F2. Finally, miR-214 overexpression inhibits glioma cell growth in vitro and in vivo by inducing cell cycle arrest in G0/G1. Collectively, these data uncover a novel role for a PPARα-miR-214-E2F2 pathway in controlling glioma cell proliferation.

scholarly journals ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xiaonan Xi ◽  
Ning Liu ◽  
Qianqian Wang ◽  
Yahui Chu ◽  
Zheng Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Synergistic Effect ◽  
Glioma Cell ◽  
Synergistic Effects ◽  
Akt Pathway ◽  
Phase I Clinical Trials ◽  
Glioma Cell Proliferation ◽  
Pai 1

Abstract PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.

402 The endogenous EPO/EPOR system contributes to glioma cell proliferation both in vitro and in vivo

2010 ◽  
Vol 8 (5) ◽  
pp. 103
Author(s):  
E. Pérès ◽  
S. Valable ◽  
J.S. Guillamo ◽  
J.F. Bernaudin ◽  
S. Roussel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Glioma Cell Proliferation

ZFX regulates glioma cell proliferation and survival in vitro and in vivo

2013 ◽  
Vol 112 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Zhichuan Zhu ◽  
Kui Li ◽  
Dafeng Xu ◽  
Yongjie Liu ◽  
Hailiang Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Glioma Cell Proliferation

scholarly journals TCTP promotes glioma cell proliferation in vitro and in vivo via enhanced  -catenin/TCF-4 transcription

2013 ◽  
Vol 16 (2) ◽  
pp. 217-227 ◽  
Author(s):  
X. Gu ◽  
L. Yao ◽  
G. Ma ◽  
L. Cui ◽  
Y. Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Glioma Cell Proliferation ◽  
Proliferation In Vitro

scholarly journals Transactivation by Retinoid X Receptor–Peroxisome Proliferator-Activated Receptor γ (PPARγ) Heterodimers: Intermolecular Synergy Requires Only the PPARγ Hormone-Dependent Activation Function

1998 ◽  
Vol 18 (6) ◽  
pp. 3483-3494 ◽  
Author(s):  
Ira G. Schulman ◽  
Gang Shao ◽  
Richard A. Heyman
Keyword(s):  
Rna Polymerase Ii ◽  
Common Property ◽  
Cultured Cells ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Activation Domain ◽  
Simultaneous Treatment ◽  
Peroxisome Proliferator Activated Receptor

ABSTRACT The ability of DNA sequence-specific transcription factors to synergistically activate transcription is a common property of genes transcribed by RNA polymerase II. The present work characterizes a unique form of intermolecular transcriptional synergy between two members of the nuclear hormone receptor superfamily. Heterodimers formed between peroxisome proliferator-activated receptor γ (PPARγ), an adipocyte-enriched member of the superfamily required for adipogenesis, and retinoid X receptors (RXRs) can activate transcription in response to ligands specific for either subunit of the dimer. Simultaneous treatment with ligands specific for both PPARγ and RXR has a synergistic effect on the transactivation of reporter genes and on adipocyte differentiation in cultured cells. Mutation of the PPARγ hormone-dependent activation domain (named τc or AF-2) inhibits the ability of RXR-PPARγ heterodimers to respond to ligands specific for either subunit. In contrast, the ability of RXR- and PPARγ-specific ligands to synergize does not require the hormone-dependent activation domain of RXR. The results of in vitro and in vivo experiments indicate that binding of ligands to RXR alters the conformation of the dimerization partner, PPARγ, and modulates the activity of the heterodimer in a manner independent of the RXR hormone-dependent activation domain.

scholarly journals Parvin-β Inhibits Breast Cancer Tumorigenicity and Promotes CDK9-Mediated Peroxisome Proliferator-Activated Receptor Gamma 1 Phosphorylation

2007 ◽  
Vol 28 (2) ◽  
pp. 687-704 ◽  
Author(s):  
Cameron N. Johnstone ◽  
Perry S. Mongroo ◽  
A. Sophie Rich ◽  
Michael Schupp ◽  
Mark J. Bowser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

ABSTRACT Parvin-β is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-β contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-β expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-β, was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Interestingly, Parvin-β reexpression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ), and there was a concomitant increase in lipogenic gene expression as a downstream effector of PPARγ. Importantly, Parvin-β suppressed breast cancer growth in vivo, with associated decreased proliferation. These data suggest that Parvin-β might influence breast cancer progression.

Controversy: PPARγ as a target for treatment of colorectal cancer

2002 ◽  
Vol 283 (2) ◽  
pp. G266-G269 ◽  
Author(s):  
Rajnish A. Gupta ◽  
Raymond N. Dubois
Keyword(s):  
Colorectal Cancer ◽  
Xenograft Model ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Loss Of Function ◽  
Preneoplastic Lesions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mouse Xenograft Model

Colorectal cancer (CRC) represents a significant cause of morbidity and mortality worldwide. Recently, ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) have exhibited promise in the treatment of CRC. For example, activation of PPARγ reduces the proliferation of cultured CRC cells grown in vitro or in vivo using the nude mouse xenograft model of tumor growth. Furthermore, agonists of the receptor also reduce the development of preneoplastic lesions in a model of carcinogen-induced CRC in rats. However, ligands for the receptor paradoxically enhance intestinal adenoma formation in another murine model of intestinal polyposis, the APC Min mice. These disparate results may be due to the inherent limitations of the APC Min mouse as a model for humans with CRC. Finally, genetic studies identifying loss of function mutations of PPARγ in human CRC specimens strongly suggest a tumor suppressive role for the receptor during the development of CRC.

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