The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Laboratory of Pathogenic Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
J Cell Mol Med. 2021 Sep;25(17):8479-8489. doi: 10.1111/jcmm.16809. Epub 2021 Aug 4.
Scutellarin, an active flavone extracted from Erigeron breviscapus, is known to exhibit antitumour activity in many cancers. However, the effects of Scutellarin on osteosarcoma remain unclear. In this study, we found that Scutellarin suppressed osteosarcoma cell growth, induced cell apoptosis and inhibited tumorigenesis. Mechanistically, our data revealed that EGR1 was significantly increased under Scutellarin treatment. Increased EGR1 enhanced tumour-suppressive effects of Scutellarin on osteosarcoma cells via transcriptionally downregulating LINC00857 expression. Additionally, we found that LINC00857 acted as a competitive endogenous RNA of miR-150-5p and inhibited the activity of miR-150-5p, which resulted in c-Myc increase. Scutellarin could suppress c-Myc protein levels through decreasing LINC00857 expression in osteosarcoma. Thus, these findings demonstrate that EGR1/ LINC00857/miR-150-5p/c-Myc axis plays a key role in promoting anticancer effects of Scutellarin and Scutellarin might have potential clinical implication in osteosarcoma clinical treatment.
野黄芩苷是从灯盏花中提取的一种黄酮类化合物，具有抗肿瘤活性，可用于多种癌症的治疗。然而，野黄芩苷对骨肉瘤的作用机制仍不清楚。在本研究中，我们发现野黄芩苷可抑制骨肉瘤细胞生长，诱导细胞凋亡，抑制肿瘤发生。机制研究表明，野黄芩苷处理可显著上调 EGR1 的表达。增加的 EGR1 通过转录下调 LINC00857 的表达增强了野黄芩苷对骨肉瘤细胞的肿瘤抑制作用。此外，我们发现 LINC00857 作为 miR-150-5p 的竞争性内源性 RNA，抑制 miR-150-5p 的活性，导致 c-Myc 增加。野黄芩苷通过降低 LINC00857 的表达来抑制 c-Myc 蛋白水平。因此，这些发现表明 EGR1/LINC00857/miR-150-5p/c-Myc 轴在促进野黄芩苷的抗癌作用中起关键作用，野黄芩苷可能在骨肉瘤的临床治疗中有潜在的应用价值。
