Department of Oncology, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xi-Cheng District, Beijing, 100050, China.
BMC Cancer. 2023 Apr 11;23(1):335. doi: 10.1186/s12885-023-10816-3.
Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment.
Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein-protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRT‒PCR were performed to explore the mechanisms.
SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)‒related genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3β/GSK3β were elevated through nongenic crosstalk regulation of the PPARs pathway.
SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.
过氧化物酶体增殖物激活受体 (PPARs) 是一个与脂肪酸 (FA) 代谢和肿瘤进展密切相关的核激素受体超家族。溶质载体家族 27 成员 2 (SLC27A2) 对 FA 转运和代谢很重要，并且与癌症进展有关。本研究旨在探讨 PPARs 和 SLC27A2 如何调节结直肠癌 (CRC) 中 FA 代谢的机制，并为 CRC 治疗寻找新策略。
应用生物信息学分析检测 PPARs 和 SLC27A2 在 CRC 中的表达和相关性。使用 STRING 数据库探索蛋白质-蛋白质相互作用 (PPI) 网络。摄取实验和免疫荧光染色分别用于分析过氧化物酶体的功能和数量以及 FA 与过氧化物酶体的共定位。Western blot 和 qRT-PCR 用于探索机制。
SLC27A2 在 CRC 中过表达。PPARs 表达水平不同，PPARG 在 CRC 中显著高表达。SLC27A2 与 CRC 中的 PPARs 相关。SLC27A2 和 PPARs 均与脂肪酸氧化 (FAO) 相关基因密切相关。SLC27A2 影响三磷酸腺苷结合盒亚家族 D 成员 3 (ABCD3) 的活性，也称为 PMP70，这是最丰富的过氧化物酶体膜蛋白。我们发现，PPARs 通路的非基因串扰调节导致 p-Erk/Erk 和 p-GSK3β/GSK3β 的比值升高。
SLC27A2 通过 PPARs 通路的非基因串扰调节在 CRC 中介导 FA 的摄取和β氧化。靶向 SLC27A2/FATP2 或 PPARs 可能为抗肿瘤策略提供新的见解。
