Central Lab of Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles HealthCare System, Los Angeles, CA, USA.
Mol Nutr Food Res. 2018 Mar;62(6):e1700844. doi: 10.1002/mnfr.201700844. Epub 2018 Feb 27.
Short-chain fatty acid sodium butyrate (NaB) is the byproduct of bacterial anaerobic fermentation of dietary fiber in the colon, and has been shown to have an antitumor effect on colorectal cancer (CRC). The miR-200 family is a key regulator of the epithelial-mesenchymal transition (EMT). We investigate the role of miR-200s expression on cell migration in NaB-treated CRC cells.
HCT116 and LOVO CRC cells treated with NaB depicted reduced cell proliferation, enhanced apoptosis, and cell cycle arrest. NaB inhibited cell migration in the wound healing and transwell assays, and in spheriod cultures while regulating EMT-related protein expression. NaB reciprocally increased miR-200s but reduced expression of their target genes (Bmi-1, Zeb1, EZH2). Cells transfected with miR-200c shRNA displayed a significant blockade of NaB-induced anti-invasive activity. Upregulation of Bmi-1 expression partially reversed the effect of NaB. In addition to inhibition of tumor growth in vivo, qRT-PCR results showed that NaB increased miR-200c/200b/492 expression in the tumor tissues. Immunohistochemistry and Western blotting results demonstrated that NaB decreased Bmi-1 expression in vivo.
NaB inhibits CRC cell migration by enhancing miR-200c expression-mediated downregulation of Bmi-1. These findings support the utility of NaB in colorectal cancer therapy.
短链脂肪酸丁酸钠（NaB）是肠道中膳食纤维细菌厌氧发酵的副产物，已被证明对结直肠癌（CRC）具有抗肿瘤作用。miR-200 家族是上皮-间充质转化（EMT）的关键调节因子。我们研究了 miR-200s 表达在 NaB 处理的 CRC 细胞中对细胞迁移的作用。
用 NaB 处理的 HCT116 和 LOVO CRC 细胞显示出细胞增殖减少、凋亡增强和细胞周期停滞。NaB 抑制划痕愈合和 Transwell 测定以及球体培养中的细胞迁移，同时调节 EMT 相关蛋白表达。NaB 反向上调 miR-200s，但降低其靶基因（Bmi-1、Zeb1、EZH2）的表达。用 miR-200c shRNA 转染的细胞显示出对 NaB 诱导的抗侵袭活性的显著阻断。Bmi-1 表达的上调部分逆转了 NaB 的作用。除了体内抑制肿瘤生长外，qRT-PCR 结果还表明 NaB 增加了肿瘤组织中 miR-200c/200b/492 的表达。免疫组织化学和 Western blot 结果表明 NaB 体内降低了 Bmi-1 的表达。
NaB 通过增强 miR-200c 表达介导的 Bmi-1 下调抑制 CRC 细胞迁移。这些发现支持 NaB 在结直肠癌治疗中的应用。
