miR-29a-3p 依赖性 COL3A1 和 COL5A1 表达降低有助于萝卜硫素抑制胃癌进展。
miR-29a-3p-dependent COL3A1 and COL5A1 expression reduction assists sulforaphane to inhibit gastric cancer progression.
机构信息
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung City 402, Taiwan; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 404, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; College of Food and Biological Engineering, Jimei University, Xiamen City 361021 Fujia Province, PR China; Undergraduate Program Study of Biomedical Engineering, Physics Department, Airlangga University, Surabaya City 60115, Indonesia.
出版信息
Biochem Pharmacol. 2021 Jun;188:114539. doi: 10.1016/j.bcp.2021.114539. Epub 2021 Apr 2.
The antitumor properties of cruciferous vegetables are mainly due to their high content of isothiocyanates, and sulforaphane (SFA) is the most well-known compound. The aim of this study was to determine the mechanism of SFA inhibiting gastric cancer (GC) progression. After verifying SFA suppressing GC growth in vivo, we utilized the GSE79973 and GSE118916 datasets to identify the GC development signatures that overlap with the RNA-seq analysis in SFA-treated AGS cells. GSEA of the RNA-seq data indicated that SFA regulation of GC progression was related to extracellular matrix and collagens; thus, we identified COL3A1 and COL5A1 as the targets of SFA, which functioned as oncogenes. We found positive correlations between COL3A1 and COL5A1 expression in GC cells, and confirmed that miR-29a-3p is the common regulator of their expression. RNA immunoprecipitation assays based on Ago2, Dicer, and exportin-5 showed that SFA could promote mature miR-29a-3p generation. We also proved that SFA inactivated the Wnt/β-catenin pathway in GC cells in a miR-29a-3p-dependent manner. Overall, SFA boosts miR-29a-3p maturation to downregulate COL3A1 and COL5A1 and inactivate the Wnt/ β -catenin pathway to suppress GC progression.
十字花科蔬菜的抗肿瘤特性主要归因于其高含量的异硫氰酸酯，而萝卜硫素（SFA）是最著名的化合物。本研究旨在确定 SFA 抑制胃癌（GC）进展的机制。在体内验证 SFA 抑制 GC 生长后，我们利用 GSE79973 和 GSE118916 数据集来鉴定与 SFA 处理的 AGS 细胞中的 RNA-seq 分析重叠的 GC 发展特征。RNA-seq 数据的 GSEA 表明，SFA 对 GC 进展的调控与细胞外基质和胶原有关；因此，我们确定 COL3A1 和 COL5A1 是 SFA 的靶标，它们作为癌基因发挥作用。我们发现 GC 细胞中 COL3A1 和 COL5A1 的表达之间存在正相关关系，并证实 miR-29a-3p 是它们表达的共同调节剂。基于 Ago2、Dicer 和 exportin-5 的 RNA 免疫沉淀测定表明，SFA 可以促进成熟的 miR-29a-3p 的产生。我们还证明 SFA 以 miR-29a-3p 依赖的方式使 GC 细胞中的 Wnt/β-catenin 通路失活。总的来说，SFA 促进 miR-29a-3p 的成熟，下调 COL3A1 和 COL5A1，并使 Wnt/β-catenin 通路失活，从而抑制 GC 进展。
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