Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Aging (Albany NY). 2020 Nov 21;13(4):4986-4998. doi: 10.18632/aging.103916.
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China. Recent studies have shown fatty acid metabolism is involved in the progression of various cancers through regulating the function of various types of cells. However, the relationship between fatty acid metabolism and tumorigenesis of ESCC remains unclear. Here, in this study, the expression of FBP1 was dramatically decreased in ESCC tissues compared with the adjacent non-ESCC tissues. The cell proliferation, migration, invasion and fatty acid metabolism were evaluated in ESCC cells using transfection of shFBP1 vectors. We found loss of FBP1 promoted ESCC cell proliferation, migration and invasion, which correlated with the activated fatty acid metabolism . Moreover, the content of phospholipids, triglycerides, neutral lipids and the protein expression levels of fatty acid metabolism related FASN, ACC1 and SREBP1C proteins were significantly increased following down-regulation of FBP1. Furthermore, FBP1 was found to be directly targeted by miR-18b-5p in ESCC cells. In addition, miR-18b-5p inhibitor treatment obviously reversed the increased fatty acid metabolism induced by loss of FBP1 in ESCC cells. These findings explored a detailed molecular mechanism of tumorigenesis and progression of ESCC and might provide a potential novel method to treat ESCC in clinic.
食管鳞状细胞癌(ESCC)是中国最常见的癌症之一。最近的研究表明,脂肪酸代谢通过调节各种类型细胞的功能参与了多种癌症的进展。然而,脂肪酸代谢与 ESCC 肿瘤发生之间的关系尚不清楚。在本研究中,与相邻的非 ESCC 组织相比,ESCC 组织中 FBP1 的表达明显降低。通过转染 shFBP1 载体,评估了 FBP1 缺失对 ESCC 细胞增殖、迁移和侵袭的影响以及脂肪酸代谢的变化。我们发现 FBP1 的缺失促进了 ESCC 细胞的增殖、迁移和侵袭,这与激活的脂肪酸代谢有关。此外,下调 FBP1 后,磷脂、甘油三酯、中性脂质的含量以及脂肪酸代谢相关 FASN、ACC1 和 SREBP1C 蛋白的表达水平均显著增加。此外,在 ESCC 细胞中发现 FBP1 是由 miR-18b-5p 直接靶向的。此外,miR-18b-5p 抑制剂处理明显逆转了 FBP1 缺失引起的 ESCC 细胞中脂肪酸代谢的增加。这些发现探索了 ESCC 发生和进展的详细分子机制,并可能为临床治疗 ESCC 提供一种新的潜在方法。