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PPAR? regulated CIDEA affects pro-apoptotic responses in glioblastoma.

ABSTRACT: Refractoriness of glioblastoma multiforme (GBM) to current treatment paradigms has necessitated identification of new targets to better the existing therapeutic strategies. One such target is peroxisome proliferator-activated receptor gamma (PPAR?) - a transcription factor involved in regulation of lipid metabolism and inflammation. Expression of PPAR?, a known regulator of cell death-inducing DFFA-like effector (CIDEA), is modulated by hypoxia inducible factor (HIF-1?). While the involvement of CIDEA in lipid metabolism is known, its role in malignancies remains largely unknown. An elevated PPAR? and low CIDEA level was observed in GBM tumors as compared with surrounding non-neoplastic tissue. As reciprocal relation exists between PPAR and HIF-1?: and as HIF-1? is a key component in glioma progression, their role in regulating CIDEA expression in glioblastoma was investigated. Although HIF-1? inhibition had no effect on CIDEA expression, pharmacological inhibition of PPAR? elevated CIDEA levels. PPAR? mediated upregulation of CIDEA was accompanied by decreased recruitment of NF?B and SP1 to their predicted binding sites on CIDEA promoter. Ectopic expression of CIDEA triggered apoptosis, activated JNK, decreased HIF-1? activation and increased PPAR? levels in glioma cells. While CIDEA overexpression induced actin cytoskeletal disruption, cell cycle arrest, release of pro-inflammatory cytokine IL-6 in a JNK-dependent manner; CIDEA mediated apoptotic cell death, decreased STAT3 phosphorylation and increased p53 acetylation was JNK independent. This study highlights for the first time the existence of (i) PPAR?-CIDEA regulatory loop in glioma and (ii) novel function of CIDEA as regulator of glioma cell survival.

SUBMITTER: Chatterjee A

PROVIDER: S-EPMC4979534 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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PPARγ regulated CIDEA affects pro-apoptotic responses in glioblastoma.

Chatterjee A A Mondal P P Ghosh S S Mehta V S VS Sen E E

Cell death discovery 20151123

Refractoriness of glioblastoma multiforme (GBM) to current treatment paradigms has necessitated identification of new targets to better the existing therapeutic strategies. One such target is peroxisome proliferator-activated receptor gamma (PPARγ) - a transcription factor involved in regulation of lipid metabolism and inflammation. Expression of PPARγ, a known regulator of cell death-inducing DFFA-like effector (CIDEA), is modulated by hypoxia inducible factor (HIF-1α). While the involvement of ...[more]

PMID: 27551468

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Dataset Information

PPAR? regulated CIDEA affects pro-apoptotic responses in glioblastoma.

Publications

PPARγ regulated CIDEA affects pro-apoptotic responses in glioblastoma.

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