Tumor Biology

, Volume 37, Issue 12, pp 15483–15488 | Cite as

RETRACTED ARTICLE: miR-203 suppression in gastric carcinoma promotes Slug-mediated cancer metastasis

Original Article

Abstract

MicroRNAs (miRNAs) play critical roles in tumorigenesis and cancer metastasis. Recently, miR-203 was reported as a tumor suppressor microRNA silenced in different malignancies including hepatocellular carcinoma, prostate cancer, oral cancer, breast cancer, and hematopoietic malignancy, whereas its role in the carcinogenesis of gastric carcinoma (GC) has not been evaluated. Here, we analyzed the levels of miR-203 and Slug in the GC specimen and studied their correlation. We analyzed the binding of miR-203 to the 3′-UTR of Slug messenger RNA (mRNA) and its effects on Slug translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-203 levels in GC cells and studied their effects on the cell invasiveness in transwell cell migration assay. We found that in GC, miR-203 levels were significantly decreased and Slug levels were significantly increased. miR-203 and Slug inversely correlated in patients’ specimen. Bioinformatic analysis predicted that miR-203 may target the 3′-UTR of Slug mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-203 inhibited Slug and cell invasiveness, while depletion of miR-203 increased Slug and cell invasiveness. These data suggest that miR-203 suppression in GC promotes Slug-mediated cancer metastasis.

Keywords

Gastric carcinoma (GC) Slug miR-203 

Notes

Acknowledgments

The study is supported by National Science Foundation of China (No.: 81472293).

Conflicts of interest

None

References

  1. 1.
    Zhao X, Li X, Yuan H. MicroRNAs in gastric cancer invasion and metastasis. Frontiers in bioscience. 2013;18:803–10.CrossRefGoogle Scholar
  2. 2.
    Liu G, Jiang C, Li D, Wang R, Wang W. MiRNA-34a inhibits EGFR-signaling-dependent MMP7 activation in gastric cancer. Tumour Biol. 2014;35:9801–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Mao D, Zhang Y, Lu H, Zhang H. Molecular basis underlying inhibition of metastasis of gastric cancer by anti-VEGFa treatment. Tumour Biol. 2014;35:8217–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Ye Y, Zhou X, Li X, Tang Y, Sun Y, Fang J. Inhibition of epidermal growth factor receptor signaling prohibits metastasis of gastric cancer via downregulation of MMP7 and MMP13. Tumour Biol. 2014;35:10891–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Wu W, Ding H, Cao J, Zhang W. FBXL5 inhibits metastasis of gastric cancer through suppressing Snail1. Cell Physiol Biochem. 2015;35:1764–72.CrossRefPubMedGoogle Scholar
  6. 6.
    Xu XY, Zhang LJ, Yu YQ, Zhang XT, Huang WJ, Nie XC, et al. Down-regulated MAC30 expression inhibits proliferation and mobility of human gastric cancer cells. Cell Physiol Biochem. 2014;33:1359–68.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhou X, Xia Y, Su J, Zhang G. Down-regulation of miR-141 induced by helicobacter pylori promotes the invasion of gastric cancer by targeting STAT4. Cell Physiol Biochem. 2014;33:1003–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Cui Y, Chen J, He Z, Xiao Y. SUZ12 depletion suppresses the proliferation of gastric cancer cells. Cell Physiol Biochem. 2013;31:778–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Di Leva G, Croce CM. MiRNA profiling of cancer. Curr Opin Genet Dev. 2013;23:3–11.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of miRNA cancer therapeutics. Drug Discov Today. 2013;18:282–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Mei Q, Li F, Quan H, Liu Y, Xu H. Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo. Cancer Sci. 2014;105:755–62.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wang F, Xiao W, Sun J, Han D, Zhu Y. MiRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt phosphorylation in glioblastoma. Tumour Biol. 2014;35:8653–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2010;31:766–76.CrossRefPubMedGoogle Scholar
  14. 14.
    Wei W, Wanjun L, Hui S, Dongyue C, Xinjun Y, Jisheng Z. miR-203 inhibits proliferation of HCC cells by targeting survivin. Cell Biochem Funct. 2013;31:82–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Viticchie G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH, et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle. 2011;10:1121–31.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhu X, Er K, Mao C, Yan Q, Xu H, Zhang Y, et al. miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer. Cell Physiol Biochem. 2013;32:64–73.CrossRefPubMedGoogle Scholar
  17. 17.
    Saini S, Majid S, Yamamura S, Tabatabai L, Suh SO, Shahryari V, et al. Regulatory role of miR-203 in prostate cancer progression and metastasis. Clin Cancer Res. 2011;17:5287–98.CrossRefPubMedGoogle Scholar
  18. 18.
    Diao Y, Guo X, Jiang L, Wang G, Zhang C, Wan J, et al. miR-203, a tumor suppressor frequently down-regulated by promoter hypermethylation in rhabdomyosarcoma. J Biol Chem. 2014;289:529–39.CrossRefPubMedGoogle Scholar
  19. 19.
    Li LP, Wu WJ, Sun DY, Xie ZY, Ma YC, Zhao YG. miR-449a and CDK6 in gastric carcinoma. Oncology letters. 2014;8:1533–8.PubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of General Surgery and Center of Minimal Invasive Gastrointestinal SurgerySouthwest Hospital, The Third Military Medical UniversityChongqingChina

Personalised recommendations