School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China.
Food Funct. 2021 Jan 21;12(2):614-632. doi: 10.1039/d0fo02265a. Epub 2020 Dec 18.
Endometrial cancer (EC) is a malignancy that severely threatens women's health and there is an urgent need to find novel natural compounds as effective treatment drugs. At the same time, multi-omics analysis of cells has been widely used in basic research to find new pathogenesis and mechanisms. Due to the lack of data on the functional importance of mRNAs and miRNAs in plant-derived asparanin A (AA) induced cancer cells, the underlying mechanisms of AA on endometrial cancer (EC) Ishikawa cells were investigated using mRNA-seq and miRNA-seq, qRT-PCR, western blot, and immunohistochemistry. The combined analysis of 37 differentially expressed miRNAs (DEMs) and 489 differentially expressed genes (DEGs) with negative regulatory relationships revealed that AA not only induced apoptosis, but also triggered autophagy through endoplasmic reticulum (ER) stress and DNA damage-related pathways. 23 DEMs and 39 DEGs participated in protein processing in the endoplasmic reticulum (PPER) and p53 signaling pathways, as shown by miRNA-target gene network analyses. Among them, we concluded that miR-6236-p5, miR-1246-p5, miR-11987_L-1, PC-5p-21544, and miR-5100-p3_1ss17TC function as hub miRNAs, and their regulation may be essential for the anti-cancer activity of AA. This study may provide a comprehensive understanding of the potential anticancer regulation of AA on EC, suggesting AA as a potential candidate for dietary supplementation in cancer medication and prevention.
子宫内膜癌（EC）是一种严重威胁妇女健康的恶性肿瘤，迫切需要寻找新的天然化合物作为有效的治疗药物。同时，细胞的多组学分析已广泛应用于基础研究，以发现新的发病机制和机制。由于缺乏植物来源的天冬酰胺 A（AA）诱导癌细胞中 mRNAs 和 miRNAs 功能重要性的数据，因此使用 mRNA-seq 和 miRNA-seq、qRT-PCR、western blot 和免疫组织化学研究了 AA 对子宫内膜癌（EC）Ishikawa 细胞的潜在机制。37 个差异表达 miRNA（DEM）和 489 个差异表达基因（DEG）的负调控关系的综合分析表明，AA 不仅诱导细胞凋亡，还通过内质网（ER）应激和 DNA 损伤相关途径触发自噬。miRNA 靶基因网络分析显示，23 个 DEM 和 39 个 DEG 参与内质网（PPER）和 p53 信号通路中的蛋白加工。其中，我们得出结论，miR-6236-p5、miR-1246-p5、miR-11987_L-1、PC-5p-21544 和 miR-5100-p3_1ss17TC 作为枢纽 miRNAs 发挥作用，它们的调节可能对 AA 的抗癌活性至关重要。这项研究可能为 AA 对 EC 的潜在抗癌作用提供全面的认识，表明 AA 可能是癌症药物治疗和预防中膳食补充剂的潜在候选物。
