Peroxisome proliferator-activated receptors (PPARs) are potential drug targets for cancer therapy

Gou, Qian; Gong, Xin; Jin, Jianhua; Shi, Juanjuan; Hou, Yongzhong

doi:10.18632/oncotarget.19610

Cited by 89 publications

(63 citation statements)

References 60 publications

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“…A number of studies showed that PPARγ agonists arrest the cell cycle, thereby inhibiting inhibit cell growth in vitro and in cancer cells inoculated into experimental animals (Law et al, 1996;Altiok et al, 1997;Motomura et al, 2000;Wakino et al, 2000;Itami et al, 2001;Koga et al, 2001;Bruemmer et al, 2003;Dios et al, 2003;Srivastava et al, 2014). Thus, PPARγ agonists are candidates for cancer therapy (Gou et al, 2017). With the placental transcript analyses, we showed that the deletion altered the expression patterns of E2Fs and cyclins, which are determinants for cell cycle staging (Cuitiño et al, 2019).…”

Section: Discussionmentioning

confidence: 91%

Targeted disruption ofPparγ1promotes trophoblast endoreplication in the murine placenta

Nakano

Aochi

Hirasaki

et al. 2020

Preprint

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In murine placentas, peroxisome proliferator-activated receptor (PPAR) γ1, a nuclear receptor, is abundant at the late stage of pregnancy (E15-E16), but its functional roles are still elusive because PPARγ-full knockout embryos die early (E10). We generated mice disrupted in only Pparγ1, one of the two major mRNA splicing variants of PPARγ1. Pparγ1knockout embryos developed normally until 15.5 dpc, but their growth was retarded thereafter and they did not survive. At 15.5 dpc, in the wild-type placentas, intense PPARγimmunostaining was detected in sinusoidal trophoblast giant cells (sTGCs), a cell lineage that coordinates the maternal blood microcirculation in the labyrinth, whereas they were absent in the knockouts. Although Pparγ1-knockout placentas were normal in morphology, we observed severely dilated maternal blood sinuses in the labyrinth. The Pparγ1-knockout sTGCs had abnormally large nuclei, an enhanced endocycling phenotype, indicating insufficient differentiation. RNA-sequencing of the placentas showed increased expression of genes coding for nucleosome assembly factors. Labyrinthine gene expressions for atypical E2Fs and cyclin E, key drivers for endocycling, were increased >3-fold. These findings suggested that PPARγ1 plays a key role in endocycle termination.

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Section: Discussionmentioning

confidence: 91%

Targeted disruption ofPparγ1promotes trophoblast endoreplication in the murine placenta

Nakano

Aochi

Hirasaki

et al. 2020

Preprint

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“…Previous studies have suggested that c‐Myc, Bcl2, bFGF and VEGF are the targets of PPARγ during cancer cell proliferation . We tested the effects of miR‐27b‐3p on the mRNA expression of these downstream molecules in ATC cells.…”

Section: Resultsmentioning

confidence: 99%

miR‐27b‐3p is Involved in Doxorubicin Resistance of Human Anaplastic Thyroid Cancer Cells via Targeting Peroxisome Proliferator‐Activated Receptor Gamma

Han

Yan

et al. 2018

Basic Clin Pharma Tox

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Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumours. To investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells. Targeted inhibition of miR-27b can increase the sensitivity of SW1736/Dox and 8305C/Dox cells. Bioinformatics analysis revealed that miR-27b can directly target peroxisome proliferator-activated receptor gamma (PPARγ) within the 3' untranslated region (UTR). This was proved by the results that miR-27b-3p down-regulated the protein and mRNA levels of PPARγ. While the mutant in the core binding sites of PPARγ abolished miR-27b-3p-induced down-regulation of luciferase activity. Over-expression of PPARγ can increase the Dox sensitivity of SW1736/Dox and 8305C/Dox cells. Basic fibroblast growth factor (bFGF) might be involved in miR-27b-3p/PPARγ-regulated Dox resistance of ATC cells. The activation of p65 nuclear factor-κB (NF-κB) regulated the up-regulation of miR-27b-3p in Dox-resistant ATC cells. Collectively, our data revealed that miR-27b-3p/PPARγ is involved in the Dox resistance of human ATC cells. It suggested that targeted inhibition of miR-27b-3p might be helpful to overcome the drug resistance of ATC cells.

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“…In high-FFA diabetic rats, the accumulation of fatty acids, eicosanoids, or oxidized phospholipids activates peroxisome proliferator-activated receptors (PPARs), which are involved in lipid metabolism. PPAR are expressed in three isoforms, namely PPARα, PPARγ and PPARδ, which are encoded by different genes and form a subfamily of the nuclear receptor superfamily (34). The activation of PPARδ in the VSMcs of diabetic patients with elevated levels of FFAs is beneficial to the cardiovascular system due to its effects on lipid metabolism, insulin sensitivity and glucose homeostasis (35,36).…”

Section: Discussionmentioning

confidence: 99%

Upregulated 14‑3‑3β aggravates restenosis by promoting cell migration following vascular injury in diabetic rats with elevated levels of free fatty acids

et al. 2018

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Mono‑unsaturated free fatty acids (FFAs) can serve as a predictive indicator of vascular restenosis following interventional therapy, particularly in individuals with high‑fat diet‑induced type 2 diabetes. However, the pathogenic mechanism remains to be fully elucidated. In the present study, the levels of tyrosine 3‑monooxygenase/tryptophan 5‑monooxygenase activation protein β (YWHAB; also known as 14‑3‑3β), in vascular smooth muscle cells (VSMCs) treated with different concentrations of oleic acid (OA) were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The migration of VSMCs was examined using wound‑healing and Transwell migration assays. The protein distribution of B‑cell lymphoma 2 (BCL‑2)‑associated death promoter (BAD) in VSMCs treated with OA was examined by immunofluorescence and western blot analyses. In in vivo experiments, the carotid artery morphology of rats in different groups was assessed at 14 days post‑injury by non-invasive ultrasonographic imaging and confirmed by histological staining. The expression of YWHAB was upregulated by OA in a concentration‑dependent manner in VSMCs. In the in vivo experiments, carotid stenosis was more serious among high‑FFA diabetic rats. However, silencing of YWHAB significantly alleviated carotid neointimal hyperplasia among the diabetic rats with elevated FFA levels. In addition, YWHAB silencing alleviated the migration of OA‑treated VSMCs and increased translocation of the BAD protein from the cytoplasm to the mitochondria. In conclusion, the results showed that FFA‑induced upregulation of YWHAB was involved in neointimal hyperplasia by enhancing the migration of VSMCs following carotid artery injury. The inhibition of YWHAB may serve as a novel potential pharmacological target for preventing vascular restenosis following interventional therapy in diabetic individuals with high FFA levels.

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Peroxisome proliferator-activated receptors (PPARs) are potential drug targets for cancer therapy

Cited by 89 publications

References 60 publications

Targeted disruption ofPparγ1promotes trophoblast endoreplication in the murine placenta

Targeted disruption ofPparγ1promotes trophoblast endoreplication in the murine placenta

miR‐27b‐3p is Involved in Doxorubicin Resistance of Human Anaplastic Thyroid Cancer Cells via Targeting Peroxisome Proliferator‐Activated Receptor Gamma

Upregulated 14‑3‑3β aggravates restenosis by promoting cell migration following vascular injury in diabetic rats with elevated levels of free fatty acids

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