Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis
Abstract 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 (...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1152-9 |
| _version_ | 1818174801676599296 |
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| author | Rilei Jiang Cheng Hu Qian Li Ziyu Cheng Ling Gu Hongxiao Li Yuanyuan Guo Qirui Li Yueyang Lu Ke Li Meijuan Chen Xu Zhang |
| author_facet | Rilei Jiang Cheng Hu Qian Li Ziyu Cheng Ling Gu Hongxiao Li Yuanyuan Guo Qirui Li Yueyang Lu Ke Li Meijuan Chen Xu Zhang |
| author_sort | Rilei Jiang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-11T19:50:11Z |
| format | Article |
| id | doaj.art-1efd2314820b41d9b04b8c1a47c26f96 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-11T19:50:11Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-1efd2314820b41d9b04b8c1a47c26f962022-12-22T00:52:47ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-04-0138111610.1186/s13046-019-1152-9Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axisRilei Jiang0Cheng Hu1Qian Li2Ziyu Cheng3Ling Gu4Hongxiao Li5Yuanyuan Guo6Qirui Li7Yueyang Lu8Ke Li9Meijuan Chen10Xu Zhang11School of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineInstitute of Literature in Chinese Medicine, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineSchool of Medicine and Life Sciences, Nanjing University of Chinese MedicineAbstract 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.http://link.springer.com/article/10.1186/s13046-019-1152-9Sodium new houttuyfonate (SNH)Linc00668miR-147aNSCLCMetastasisceRNA |
| spellingShingle | Rilei Jiang Cheng Hu Qian Li Ziyu Cheng Ling Gu Hongxiao Li Yuanyuan Guo Qirui Li Yueyang Lu Ke Li Meijuan Chen Xu Zhang Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis Journal of Experimental & Clinical Cancer Research Sodium new houttuyfonate (SNH) Linc00668 miR-147a NSCLC Metastasis ceRNA |
| title | Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis |
| title_full | Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis |
| title_fullStr | Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis |
| title_full_unstemmed | Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis |
| title_short | Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis |
| title_sort | sodium new houttuyfonate suppresses metastasis in nsclc cells through the linc00668 mir 147a slug axis |
| topic | Sodium new houttuyfonate (SNH) Linc00668 miR-147a NSCLC Metastasis ceRNA |
| url | http://link.springer.com/article/10.1186/s13046-019-1152-9 |
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