Gao Zhuo, Wang Yan, Ren Zijian, Li Qiankun, Wang Ying, Dai Yifan
State Key Laboratory of Reproductive Medicine, Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Tumour Biol. 2014 Oct;35(10):9717-23. doi: 10.1007/s13277-014-2261-x. Epub 2014 Jun 28.
n-3 Polyunsaturated fatty acids (n-3 PUFAs) contribute to preventing many types of diseases, including cancer; however, a high n-6 polyunsaturated fatty acids (n-6 PUFAs) intake in modern diets has the opposite effect. Previously, we developed a transgenic mouse model that expresses a gene, fat-1, encoding an n-3 fatty acid desaturase, which converts n-6 PUFAs to n-3 PUFAs in vivo. MicroRNAs (miRNAs) in serum are stable, reproducible, and consistent among individuals of the same species and serve as potential biomarkers for the detection of cancers and other diseases. Employing illumina sequencing, we analyzed all the serum miRNAs in wild-type and mfat-1 transgenic mice. Using quantitative real-time PCR (RT-qPCR), we identified 12 miRNAs that were highly expressed in mfat-1 mice. Pathway analysis of targets regulated by these miRNAs revealed a significant number of genes involved in the development of cancer, including phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinases (MAPK), and mammalian target of rapamycin (mTOR), which suggested a relationship between n-3 PUFAs and cancer prevention.
n-3多不饱和脂肪酸（n-3 PUFAs）有助于预防多种疾病，包括癌症；然而，现代饮食中高摄入n-6多不饱和脂肪酸（n-6 PUFAs）则有相反的效果。此前，我们构建了一种转基因小鼠模型，该模型表达一种名为fat-1的基因，该基因编码一种n-3脂肪酸去饱和酶，可在体内将n-6 PUFAs转化为n-3 PUFAs。血清中的微小RNA（miRNAs）稳定、可重复，且在同一物种的个体之间具有一致性，可作为检测癌症和其他疾病的潜在生物标志物。利用Illumina测序技术，我们分析了野生型和mfat-1转基因小鼠的所有血清miRNAs。通过定量实时PCR（RT-qPCR），我们鉴定出12种在mfat-1小鼠中高表达的miRNAs。对这些miRNAs调控的靶标进行通路分析，发现大量参与癌症发生发展的基因，包括磷脂酰肌醇3激酶（PI3K）、丝裂原活化蛋白激酶（MAPK）和雷帕霉素靶蛋白（mTOR），这提示了n-3 PUFAs与癌症预防之间的关系。
