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Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism

Abstract

To observe the effects of small interfering RNA (siRNA)-targeting bone morphogenetic protein (BMP)-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism. Three siRNAs-targeting BMP-2 gene were synthesized. There were six groups including group I (non-transfected cells), group II (only liposome-transfected cells), group III (non-specific siRNA-transfected cells) and groups IV–VI (siRNA-A, siRNA-B and siRNA-C-targeting BMP-2 transfected cells, respectively). SMMC7721 cells were instantaneously transfected using lipofectamine method. The levels of mRNA and protein of BMP-2 in cells were determined with reverse transcription-PCR and western blotting. The abilities of migration and invasion of transfected cells were assessed using scratch test and in vitro invasion assay, respectively. The protein levels of p-ERK, p-JNK and p-p38 and the protein levels of MMP-2 and MMP-9 were evaluated with western blot 48 h after siRNA-B-targeting BMP-2 was transfected into liver cancer SMMC7721 cells. Expression of mRNA and protein of BMP-2 in groups IV–VI were significantly inhibited, especially in group V. Cell scratch width was significantly greater in group V than in group I and III (P<0.01). In vitro invasion assay suggested that the number of invasion of cells was significantly lower in group V than in group I and III (P<0.05). Western blot indicated that the level of p-ERK was significantly decreased (P<0.05), the levels of p-JHK and p-p38 were not significantly changed and the levels of MMP-2 and MMP-9 were significantly downregulated (P<0.05). siRNA-targeting BMP-2 can markedly inhibited the expression of BMP-2 in liver cancer SMMC7721 cells, and decrease the abilities of migration and invasion of liver cancer cells, especially siRNA-B. The inhibitory effects of siRNA-B-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells may be caused by the downregulation of MMP-2 and MMP-9 through MAPK/ERK pathway, whereas is not related to MAPK/JNK and MAPK/p38 pathway.

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References

  1. Langenfeld EM, Langenfeld J . Bone morphogenetic protein-2 stimulates angiogenesis in developing tumors. Mol Cancer Res 2004; 2: 141–149.

    CAS  PubMed  Google Scholar 

  2. Davies SR, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG . Bone morphogenetic proteins 1 to 7 in human breast cancer, expression pattern and clinical/prognostic relevance. J Exp Ther Oncol 2008; 7: 327–338.

    CAS  PubMed  Google Scholar 

  3. Tuschl T, Zamore PD, Lehman R, Bartel DP, Sharp PA . Targeted mRNA degradation by double-strand RNA in vitro. Genes & Dev 1999; 13: 3191–3197.

    Article  CAS  Google Scholar 

  4. Langenfeld EM, Calvano SE, Abou-Nukta F, Lowry SF, Amenta P, Langenfeld J . The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells. Carcinogenesis 2003; 24: 1445–1454.

    Article  CAS  PubMed  Google Scholar 

  5. Busch C, Drews U, Eisele SR, Garbe C, Oppitz M . Noggin blocks invasive growth of murine B16-F1 melanoma cells in the optic cup of the chick embryo. Int J Cancer 2008; 122: 526–533.

    Article  CAS  PubMed  Google Scholar 

  6. Rothhammer T, Poser I, Soncin F, Bataille F, Moser M, Bosserhoff AK . Bone morphogenic proteins are overexpressed in malignant melanoma and promote cell invasion and migration. Cancer Res 2005; 65: 448–456.

    CAS  PubMed  Google Scholar 

  7. Montesano R . Bone morphogenetic protein-4 abrogates lumen formation by mammary epithelial cells and promotes invasive growth. Biochem Biophys Res Commun 2007; 353: 817–822.

    Article  CAS  PubMed  Google Scholar 

  8. Deng H, Makizumi R, Ravikumar TS, Dong H, Yang W, Yang W . Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. Exp Cell Res 2007; 313: 1033–1044.

    Article  CAS  PubMed  Google Scholar 

  9. Langenfeld EM, Bojnowski J, Perone J, Langenfeld J . Expression of bone morphogenetic proteins in human lung carcinomas. Ann Thorac Surg 2005; 80: 1028–1032.

    Article  PubMed  Google Scholar 

  10. Darby S, Cross SS, Brown NJ, Hamdy FC, Robson CN . BMP-6 over-expression in prostate cancer is associated with increased Id-1 protein and a more invasive phenotype. J Pathol 2008; 214: 394–404.

    Article  CAS  PubMed  Google Scholar 

  11. Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 2006; 444: 761–765.

    Article  CAS  PubMed  Google Scholar 

  12. Busch C, Drews U, Eisele SR, Garbe C, Oppitz M . Noggin blocks invasive growth of murine B16-F1 melanoma cells in the optic cup of the chick embryo. Int J Cancer 2008; 122: 526–533.

    Article  CAS  PubMed  Google Scholar 

  13. Jian-bing Wu, Hua-qun Fu, Long-zhang H, An-wen L, Ji-xiang Z . Expression of bone morphogenetic protein 2 and 6 and clinical significance in liver carcinoma. World Chinese J Digestol 2009; 17: 834–837.

    Article  Google Scholar 

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Wu, JB., Fu, HQ., Huang, LZ. et al. Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism. Cancer Gene Ther 18, 20–25 (2011). https://doi.org/10.1038/cgt.2010.55

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  • DOI: https://doi.org/10.1038/cgt.2010.55

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