Yu Yaying, Xing Yanwei, Zhang Qian, Zhang Qianqian, Huang Shuangjian, Li Xinxin, Gao Chao
Department of Nutrition, The First Affiliated Hospital of Henan University, Kaifeng, China.
Department of Pediatrics, Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng, China.
IUBMB Life. 2021 Jan;73(1):92-107. doi: 10.1002/iub.2404. Epub 2020 Nov 7.
The foods of plants provide the rich nutrition and have protective function in human diseases, including cancers. Genistein is a major isoflavone constituent in soybeans, which has an anti-cancer role in non-small-cell lung cancer (NSCLC). Nevertheless, the mechanism underlying the anti-cancer function of genistein in NSCLC remains largely unknown. NSCLC cells (H292 and A549) were exposed to genistein. Circular RNA hsa_circ_0031250 (circ_0031250), microRNA (miR)-873-5p and forkhead box M1 (FOXM1) abundances were examined via quantitative reverse transcription polymerase chain reaction and Western blotting. The function of genistein, circ_0031250, miR-873-5p, and FOXM1 on NSCLC progression was investigated via Cell Counting Kit-8, colony formation, transwell well, wound healing, flow cytometry, Western blotting and xenograft model. The target relationship was analyzed by dual-luciferase reporter analysis and RNA immunoprecipitation. Results showed that genistein inhibited NSCLC cell viability in dose-time-dependent patterns. circ_0031250 abundance was elevated in NSCLC samples and cell lines, and it was reduced via genistein exposure. circ_0031250 knockdown aggravated genistein-caused suppression of cell proliferation, migration and invasion and elevation of apoptosis. miR-873-5p expression was decreased in NSCLC samples and cells. miR-873-5p was targeted via circ_0031250, and miR-873-5p knockdown attenuated the influence of circ_0031250 silence on NSCLC progression in the presence of genistein. FOXM1 was regulated via circ_0031250/miR-873-5p axis. miR-873-5p constrained cell proliferation, migration and invasion and increased apoptosis via regulating FOXM1 in genistein-treated cells. circ_0031250 knockdown enhanced the inhibitive function of genistein on NSCLC cell growth in xenograft model. Collectively, genistein repressed NSCLC progression by modulating circ_0031250/miR-873-5p/FOXM1 axis.
植物性食物富含营养，对包括癌症在内的人类疾病具有保护作用。染料木黄酮是大豆中的主要异黄酮成分，在非小细胞肺癌（NSCLC）中具有抗癌作用。然而，染料木黄酮在NSCLC中的抗癌作用机制仍不清楚。将NSCLC细胞（H292和A549）暴露于染料木黄酮。通过定量逆转录聚合酶链反应和蛋白质免疫印迹法检测环状RNA hsa_circ_0031250（circ_0031250）、微小RNA（miR）-873-5p和叉头框M1（FOXM1）的丰度。通过细胞计数试剂盒-8、集落形成、Transwell小室、伤口愈合、流式细胞术、蛋白质免疫印迹法和异种移植模型研究染料木黄酮、circ_0031250、miR-873-5p和FOXM1对NSCLC进展的作用。通过双荧光素酶报告基因分析和RNA免疫沉淀分析靶标关系。结果表明，染料木黄酮以剂量-时间依赖性方式抑制NSCLC细胞活力。circ_0031250在NSCLC样本和细胞系中的丰度升高，染料木黄酮处理可使其降低。circ_0031250敲低加重了染料木黄酮引起的细胞增殖、迁移和侵袭抑制以及凋亡增加。miR-873-5p在NSCLC样本和细胞中的表达降低。circ_0031250靶向miR-873-5p，在存在染料木黄酮的情况下，miR-873-5p敲低减弱了circ_0031250沉默对NSCLC进展的影响。FOXM1通过circ_0031250/miR-873-5p轴调控。在染料木黄酮处理的细胞中，miR-873-5p通过调节FOXM1抑制细胞增殖、迁移和侵袭并增加凋亡。circ_0031250敲低增强了染料木黄酮在异种移植模型中对NSCLC细胞生长的抑制作用。总之，染料木黄酮通过调节circ_0031250/miR-873-5p/FOXM1轴抑制NSCLC进展。
