PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs
Breast cancer (BC) is the most common type of cancer among females. Peroxisome proliferator-activated receptor gamma (PPARG) can regulate the production of adipocyte-related genes and has anti-inflammatory and anti-tumor effects. Our aim was to investigate PPARG expression, its possible prognostic v...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2023/4481354 |
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| author | De-Hui Li Xu-Kuo Liu Xiao-Tong Tian Fei Liu Xu-Jiong Yao Jing-Fei Dong |
| author_facet | De-Hui Li Xu-Kuo Liu Xiao-Tong Tian Fei Liu Xu-Jiong Yao Jing-Fei Dong |
| author_sort | De-Hui Li |
| collection | DOAJ |
| description | Breast cancer (BC) is the most common type of cancer among females. Peroxisome proliferator-activated receptor gamma (PPARG) can regulate the production of adipocyte-related genes and has anti-inflammatory and anti-tumor effects. Our aim was to investigate PPARG expression, its possible prognostic value, and its effect on immune cell infiltration in BC, and explore the regulatory effects of natural drugs on PPARG to find new ways to treat BC. Using different bioinformatics tools, we extracted and comprehensively analyzed the data from the Cancer Genome Atlas, Genotype-Tissue Expression, and BenCaoZuJian databases to study the potential anti-BC mechanism of PPARG and potential natural drugs targeting it. First, we found that PPARG was downregulated in BC and its expression level correlates with pathological tumor stage (pT-stage) and pathological tumor-node-metastasis stage (pTNM-stage) in BC. PPARG expression was higher in estrogen receptor-positive (ER+) BC than in estrogen receptor-negative (ER−) BC, which tends to indicate a better prognosis. Meanwhile, PPARG exhibited a significant positive correlation with the infiltration of immune cells and correlated with better cumulative survival in BC patients. In addition, PPARG levels were shown to be positively associated with the expression of immune-related genes and immune checkpoints, and ER+ patients had better responses to immune checkpoint blocking. Correlation pathway research revealed that PPARG is strongly associated with pathways, such as angiogenesis, apoptosis, fatty acid biosynthesis, and degradation in ER+ BC. We also found that quercetin is the most promising natural anti-BC drug among natural medicines that upregulate PPARG. Our research showed that PPARG may reduce BC development by regulating the immune microenvironment. Quercetin as PPARG ligands/agonists is a potential natural drug for BC treatment. |
| format | Article |
| id | doaj-art-ce11480b187746a6bdf2f5787a1b5eac |
| institution | DOAJ |
| issn | 1687-4765 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-ce11480b187746a6bdf2f5787a1b5eac2025-08-20T03:05:01ZengWileyPPAR Research1687-47652023-01-01202310.1155/2023/4481354PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural DrugsDe-Hui Li0Xu-Kuo Liu1Xiao-Tong Tian2Fei Liu3Xu-Jiong Yao4Jing-Fei Dong5The First Affiliated Hospital of Hebei University of Chinese MedicineGraduate School of Hebei University of Chinese MedicineGraduate School of Hebei University of Chinese MedicineHebei University of Chinese MedicineThe First Affiliated Hospital of Hebei University of Chinese MedicineThe First Affiliated Hospital of Hebei University of Chinese MedicineBreast cancer (BC) is the most common type of cancer among females. Peroxisome proliferator-activated receptor gamma (PPARG) can regulate the production of adipocyte-related genes and has anti-inflammatory and anti-tumor effects. Our aim was to investigate PPARG expression, its possible prognostic value, and its effect on immune cell infiltration in BC, and explore the regulatory effects of natural drugs on PPARG to find new ways to treat BC. Using different bioinformatics tools, we extracted and comprehensively analyzed the data from the Cancer Genome Atlas, Genotype-Tissue Expression, and BenCaoZuJian databases to study the potential anti-BC mechanism of PPARG and potential natural drugs targeting it. First, we found that PPARG was downregulated in BC and its expression level correlates with pathological tumor stage (pT-stage) and pathological tumor-node-metastasis stage (pTNM-stage) in BC. PPARG expression was higher in estrogen receptor-positive (ER+) BC than in estrogen receptor-negative (ER−) BC, which tends to indicate a better prognosis. Meanwhile, PPARG exhibited a significant positive correlation with the infiltration of immune cells and correlated with better cumulative survival in BC patients. In addition, PPARG levels were shown to be positively associated with the expression of immune-related genes and immune checkpoints, and ER+ patients had better responses to immune checkpoint blocking. Correlation pathway research revealed that PPARG is strongly associated with pathways, such as angiogenesis, apoptosis, fatty acid biosynthesis, and degradation in ER+ BC. We also found that quercetin is the most promising natural anti-BC drug among natural medicines that upregulate PPARG. Our research showed that PPARG may reduce BC development by regulating the immune microenvironment. Quercetin as PPARG ligands/agonists is a potential natural drug for BC treatment.http://dx.doi.org/10.1155/2023/4481354 |
| spellingShingle | De-Hui Li Xu-Kuo Liu Xiao-Tong Tian Fei Liu Xu-Jiong Yao Jing-Fei Dong PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs PPAR Research |
| title | PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs |
| title_full | PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs |
| title_fullStr | PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs |
| title_full_unstemmed | PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs |
| title_short | PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs |
| title_sort | pparg a promising therapeutic target in breast cancer and regulation by natural drugs |
| url | http://dx.doi.org/10.1155/2023/4481354 |
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