Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a
Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a
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DOI：
10.1038/s41598-019-45924-3
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发表时间：
2019-07-01
影响因子：
4.6
通讯作者：
Hong, Suntaek
中科院分区：
文献类型：
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作者：
Kim, Hye-Youn;Kim, Young-Mi;Hong, Suntaek
结直肠癌(CRC)是第三大常见癌症，在全球癌症相关死亡中所占比例很高。此外，结直肠癌治疗的成功率主要取决于转移情况。因此，需要寻找新的药物或治疗技术来治疗转移性结直肠癌。本研究通过对AXT进行高通量药物筛选，筛选出最常见的类胡萝卜素之一虾青素(AXT)作为一种新型的肿瘤转移抑制药物，并证实了AXT的抗迁移和抗侵袭活性。我们发现，AXT可上调miR-29a-3p和miR-200a的表达，从而分别抑制MMP2和ZEB1的表达。因此，AXT抑制了结直肠癌细胞上皮-间充质转化(EMT)。通过机制研究，我们发现AXT通过转录抑制MYC转录因子发挥抗肿瘤转移的作用。最后，我们还利用小鼠模型证实了AXT抑制结肠癌细胞的体内转移能力。总而言之，我们揭示了AXT在抑制EMT和内陷形成方面的新功能，暗示了AXT在转移性结直肠癌患者中的新治疗潜力。
Colorectal cancer (CRC) is the third most common cancer, and is associated with a high percentage of cancer-related death globally. Furthermore, the success rate of therapeutic treatment for CRC patients mainly depends on the status of metastasis. Therefore, novel drugs or therapeutic techniques should be discovered for the treatment of metastatic CRC. In this study, we selected Astaxanthin (AXT), one of the most common carotenoids, as a novel metastasis inhibitor through high-throughput drug screening based on invadopodia staining, and confirmed the anti-migratory and anti-invasive activity of AXT. We demonstrated that AXT increases miR-29a-3p and miR-200a expression, and thereby suppresses the expression of MMP2 and ZEB1, respectively. As a result, AXT represses the epithelial-mesenchymal transition (EMT) of CRC cells. Through the mechanistic study, we identified that AXT shows anti-metastatic activity through the transcriptional repression of MYC transcription factor. Finally, we also confirmed that AXT suppresses the in vivo metastatic capacity of colon cancer cell using mouse model. Collectively, we uncovered the novel function of AXT in the inhibition of EMT and invadopodia formation, implicating the novel therapeutic potential for AXT in metastatic CRC patients.