Qiu Shi, Zhang Aihua, Zhang Tianlei, Sun Hui, Guan Yu, Yan Guangli, Wang Xijun
Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Heilongjiang University of Chinese Medicine, Harbin, China.
Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China.
Oncotarget. 2017 Oct 19;8(65):108760-108770. doi: 10.18632/oncotarget.21897. eCollection 2017 Dec 12.
A multi-omics approach could yield in-depth mechanistic insights. Here, we performed an integrated analysis of miRNAome, proteome and metabolome, aimed to investigate the underlying mechanism of active product geniposide in ethanol-induced apoptosis. We found that integrative meta-analysis identified 28 miRNAs, 20 proteins and 7 metabolites significantly differentially expressed, respectively. Further analysis identified geniposide extensively regulated multiple metabolism pathways and the most important related pathway was citrate cycle (TCA cycle). In addition, geniposide can improve energy metabolism benefits using the Extracellular Flux Analyzer. Of particular significance, miR-144-5p exhibits a high positive correlation with oxoglutaric acid, isocitrate dehydrogenase (IDH) 1 and 2 that involved in the TCA cycle. Furthermore,we discovered that miR-144-5p regulates TCA cycle metabolism through IDH1 and IDH2. Collectively, we describe for the first time the hepatoprotective effect of geniposide decreased miR-144-5p level, capable of regulating TCA cycle by directly targeting IDH1 and IDH2 and promoting functional consequences in cells. Integrating metabolomics, miRNAomics and proteomics approach and thereby analyzing microRNAs and proteins as well as metabolites can give valuable information about the functional regulation pattern and action mechanism of natural products.
多组学方法可以产生深入的机制性见解。在此，我们对miRNA组、蛋白质组和代谢组进行了综合分析，旨在研究活性产物京尼平苷在乙醇诱导的细胞凋亡中的潜在机制。我们发现，整合荟萃分析分别鉴定出28个miRNA、20种蛋白质和7种代谢物有显著差异表达。进一步分析发现，京尼平苷广泛调节多种代谢途径，其中最重要的相关途径是柠檬酸循环（三羧酸循环）。此外，使用细胞外通量分析仪发现京尼平苷可以改善能量代谢益处。特别值得注意的是，miR-144-5p与参与三羧酸循环的氧代戊二酸、异柠檬酸脱氢酶（IDH）1和2呈现高度正相关。此外，我们发现miR-144-5p通过IDH1和IDH2调节三羧酸循环代谢。总体而言，我们首次描述了京尼平苷降低miR-144-5p水平的肝脏保护作用，其能够通过直接靶向IDH1和IDH2调节三羧酸循环并在细胞中产生功能性结果。整合代谢组学、miRNA组学和蛋白质组学方法，从而分析miRNA、蛋白质以及代谢物，可以提供有关天然产物功能调节模式和作用机制的有价值信息。
