PPARG Could Work as a Valid Therapeutic Strategy for the Treatment of Lung Squamous Cell Carcinoma

Shi, Sixiang; Yu, Guiping; Huang, Bin; Mi, Yedong; Kang, Yan; Simon, Julia Pia

doi:10.1155/2020/2510951

Cited by 17 publications

(15 citation statements)

References 44 publications

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“…Increasing evidence has indicated that PPAR-g agonists may serve as master modulators for overcoming classic obstacles associated with targeted NSCLC therapies, including resistance to therapy and tumor genetic heterogeneity (144)(145)(146). These examples strongly suggest that PPAR-g has potential as a molecular target for NSCLC treatment (129,(147)(148)(149).…”

Section: Pgc-1a/ppar-g Signaling In Hypoxia-induced Chemoresistance In Nsclcmentioning

confidence: 99%

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Luo

et al. 2021

Front. Oncol.

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Resistance is the major cause of treatment failure and disease progression in non-small cell lung cancer (NSCLC). There is evidence that hypoxia is a key microenvironmental stress associated with resistance to cisplatin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and immunotherapy in solid NSCLCs. Numerous studies have contributed to delineating the mechanisms underlying drug resistance in NSCLC; nevertheless, the mechanisms involved in the resistance associated with hypoxia-induced molecular metabolic adaptations in the microenvironment of NSCLC remain unclear. Studies have highlighted the importance of posttranslational regulation of molecular mediators in the control of mitochondrial function in response to hypoxia-induced metabolic adaptations. Hypoxia can upregulate the expression of sirtuin 1 (SIRT1) in a hypoxia-inducible factor (HIF)-dependent manner. SIRT1 is a stress-dependent metabolic sensor that can deacetylate some key transcriptional factors in both metabolism dependent and independent metabolic pathways such as HIF-1α, peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-gamma coactivator 1-alpha (PGC-1α) to affect mitochondrial function and biogenesis, which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and HIF-1α can regulate both innate and adaptive immune responses through metabolism-dependent and -independent ways. The objective of this review is to delineate a possible SIRT1/PGC-1α/PPAR-γ signaling-related molecular metabolic mechanism underlying hypoxia-induced chemotherapy resistance in the NSCLC microenvironment. Targeting hypoxia-related metabolic adaptation may be an attractive therapeutic strategy for overcoming chemoresistance in NSCLC.

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Section: Pgc-1a/ppar-g Signaling In Hypoxia-induced Chemoresistance In Nsclcmentioning

confidence: 99%

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Luo

et al. 2021

Front. Oncol.

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“…PPARs are ligand-activated transcription factors which belong to the nuclear receptor superfamily including PPARα, PPARβ/δ, and PPARγ three isoforms [5,6]. PPARs interact with other transcription regulators to regulate the transcription of its target genes involved in energy metabolism and important cellular biological functions like inflammation, cellular proliferation, and differentiation [7,8].…”

Section: Introductionmentioning

confidence: 99%

DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer

Zhao

Zhong²,

Lü

et al. 2021

PPAR Research

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Ovarian carcinoma (OV) is a lethal gynecological malignancy. Most OV patients develop resistance to platinum-based chemotherapy and recurrence. Peroxisome proliferator-activated receptors (PPARs) are the ligand activating transcription factor of the nuclear receptor superfamily. PPARs as important transcriptional regulators regulate important physiological processes such as lipid metabolism, inflammation, and wound healing. Several reports point out that PPARs can also have an effect on the sensitivity of tumor cells to platinum-based chemotherapy drugs. However, the role of PPAR-target related genes (PPAR-TRGs) in chemotherapeutic resistance of OV remains unclear. The present study is aimed at optimizing candidate genes by integrating platinum-chemotherapy expression data and PPAR family genes with their targets. The gene expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. A total of 4 genes (AP2A2, DOCK4, HSDL2, and PDK4) were the candidate differentially expressed genes (DEGs) of PPAR-TRGs with platinum chemosensitivity. After conducting numerous survival analyses using different cohorts, we found that only the upexpression of DOCK4 has important significance with the poor prognosis of OV patients. Meanwhile, DOCK4 is detected in plasma and enriched in neutrophil and monocyte cells of the blood. We further found that there were significant correlations between DOCK4 expression and the levels of CD4+ T cell infiltration, dendritic cell infiltration, and neutrophil infiltration in OV. In addition, we verified the expression level of DOCK4 in OV cell lines treated with platinum drugs and found that DOCK4 is potentially responsive to platinum drugs. In conclusion, DOCK4 is potentially associated with immune cell infiltration and represents a valuable prognostic biomarker in ovarian cancer patients.

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“…Silencing of NFIX expression can inhibit the proliferation, migration, and invasion of lung cancer cell lines [ 14 ]. Studies have shown that activation of peroxisome proliferator-activated receptor-gamma (PPARGγ) may inhibit the progression of lung squamous cell carcinoma (LSCC) through the regulation of upstream and downstream marker genes of LSCC, and these genes are involved in tumor-cell proliferation and protein polyubiquitination/ubiquitination [ 15 ]. Inositol 1,4,5-trisphosphate 3-kinase (ITPKA), a member of the inositol polyphosphate kinase (IPK) family, regulates the level of inositol polyphosphate, which is critical for transduction of cell signals.…”

Section: Discussionmentioning

confidence: 99%

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes

et al. 2021

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We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan–Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.

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PPARG Could Work as a Valid Therapeutic Strategy for the Treatment of Lung Squamous Cell Carcinoma

Cited by 17 publications

References 44 publications

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes

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