School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Institute of Literature in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
J Exp Clin Cancer Res. 2019 Apr 11;38(1):155. doi: 10.1186/s13046-019-1152-9.
As most lung cancer patients present with invasive, metastatic disease, it is vital to investigate anti-metastatic treatments for non-small cell lung cancer (NSCLC). Houttuynia cordata is commonly used as a Chinese anticancer medicine in the clinic, and sodium new houttuyfonate (SNH), a main compound of this herb, has long been found to have antibiotic effects, although its anticancer effects have not been investigated. Here, we tried to address this lack of research from the perspective of the competing endogenous RNA (ceRNA) theory.
The effects of SNH on NSCLC cells were analysed with Cell Counting Kit-8 assays and colony formation assays. In addition, transwell assays and wound healing assays were used to determine the effects of SNH on migration and invasion in NSCLC cells. The levels of key genes and proteins were examined by quantitative real-time PCR, western blotting, immunofluorescence staining and IHC staining. Through transcriptome screening and digital gene expression profiling, Linc00668 was identified to be regulated by SNH. Dual-luciferase reporter assays and RNA immunoprecipitation assays verified the binding efficiency between miR-147a and Linc00668 or Slug.
In the present study, SNH regulated NSCLC cells in multiple ways, the most prominent of which was suppressing the expression of Linc00668, which was indicated to promote migration and invasion in NSCLC cells. Functional studies demonstrated that Linc00668 acted as a ceRNA by sponging miR-147a to further regulate Slug mRNA levels, thereby influencing the progression of the epithelial-mesenchymal transition. Consistently, the results of in vivo animal models showed that SNH depressed Linc00668 and suppressed the metastasis of NSCLC.
SNH suppressed metastasis of NSCLC cells and the mechanism may involve with the Linc00668/miR-147a/Slug axis.
由于大多数肺癌患者表现为侵袭性、转移性疾病，因此研究非小细胞肺癌（NSCLC）的抗转移治疗至关重要。鱼腥草在临床上常被用作一种抗癌中药，其主要成分之一新鱼腥草素钠（SNH）长期以来一直被发现具有抗生素作用，尽管其抗癌作用尚未得到研究。在这里，我们试图从竞争内源性 RNA（ceRNA）理论的角度来解决这一缺乏研究的问题。
用细胞计数试剂盒-8 检测和集落形成检测分析 SNH 对 NSCLC 细胞的影响。此外，还使用 Transwell 检测和划痕愈合检测来确定 SNH 对 NSCLC 细胞迁移和侵袭的影响。通过定量实时 PCR、western blot、免疫荧光染色和免疫组化染色检测关键基因和蛋白的水平。通过转录组筛选和数字基因表达谱分析，鉴定出 SNH 调节的 Linc00668。双荧光素酶报告基因检测和 RNA 免疫沉淀检测验证了 miR-147a 与 Linc00668 或 Slug 之间的结合效率。
在本研究中，SNH 以多种方式调节 NSCLC 细胞，最显著的是抑制 Linc00668 的表达，这表明 Linc00668 促进 NSCLC 细胞的迁移和侵袭。功能研究表明，Linc00668 作为 ceRNA 通过海绵吸附 miR-147a 进一步调节 Slug mRNA 水平，从而影响上皮-间充质转化的进展。同样，体内动物模型的结果表明，SNH 抑制了 Linc00668 的表达并抑制了 NSCLC 的转移。
SNH 抑制 NSCLC 细胞的转移，其机制可能涉及 Linc00668/miR-147a/Slug 轴。
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