Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
SNH suppressed metastasis of NSCLC cells and the mechanism may involve with the Linc00668/miR-147a/Slug axis.
['Jiang|Rilei|R|', 'Hu|Cheng|C|', 'Li|Qian|Q|', 'Cheng|Ziyu|Z|', 'Gu|Ling|L|', 'Li|Hongxiao|H|', 'Guo|Yuanyuan|Y|', 'Li|Qirui|Q|', 'Lu|Yueyang|Y|', 'Li|Ke|K|', 'Chen|Meijuan|M|', 'Zhang|Xu|X|']
D000818:Animals D002289:Carcinoma, Non-Small-Cell Lung D045744:Cell Line, Tumor D004365:Drugs, Chinese Herbal D052859:Houttuynia D006801:Humans D008175:Lung Neoplasms D051379:Mice D035683:MicroRNAs D009362:Neoplasm Metastasis D014162:Transfection
Metastasis NSCLC Linc00668 miR-147a Sodium new houttuyfonate (SNH) ceRNA