PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs.

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL PPAR Research Pub Date : 2023-01-01 DOI:10.1155/2023/4481354
De-Hui Li, Xu-Kuo Liu, Xiao-Tong Tian, Fei Liu, Xu-Jiong Yao, Jing-Fei Dong
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引用次数: 1

Abstract

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.

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PPARG:一个有前景的乳腺癌治疗靶点及天然药物的调控作用。
乳腺癌(BC)是女性中最常见的癌症。过氧化物酶体增殖物激活受体γ (PPARG)可以调节脂肪细胞相关基因的产生,具有抗炎和抗肿瘤作用。我们的目的是研究PPARG在BC中的表达、可能的预后价值及其对免疫细胞浸润的影响,并探讨天然药物对PPARG的调节作用,以寻找治疗BC的新方法。我们利用不同的生物信息学工具,提取并综合分析来自Cancer Genome Atlas、Genotype-Tissue Expression和bencozujian数据库的数据,研究PPARG潜在的抗bc机制和潜在的靶向天然药物。首先,我们发现PPARG在BC中下调,其表达水平与BC的病理肿瘤分期(pt期)和病理肿瘤-淋巴结-转移分期(ptnm期)相关。PPARG在雌激素受体阳性(ER+) BC中的表达高于雌激素受体阴性(ER-) BC,这往往预示着更好的预后。同时,PPARG与BC患者免疫细胞浸润呈显著正相关,与较好的累积生存率相关。此外,PPARG水平与免疫相关基因和免疫检查点的表达呈正相关,ER+患者对免疫检查点阻断的反应更好。相关通路研究表明,PPARG与ER+ BC血管生成、细胞凋亡、脂肪酸生物合成和降解等通路密切相关。我们还发现槲皮素是上调PPARG的天然药物中最有希望的天然抗bc药物。我们的研究表明,PPARG可能通过调节免疫微环境来减少BC的发展。槲皮素作为PPARG配体/激动剂是治疗BC的潜在天然药物。
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来源期刊
PPAR Research
PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.20
自引率
3.40%
发文量
17
审稿时长
12 months
期刊介绍: PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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