Skip to main content
SpringerLink
Log in

Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting notch1

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

MicroRNAs (miRNAs or miRs) are a class of short, non-coding RNAs that participate in various oncological processes. This study aims to explore the roles of microRNA-34a (miR-34a) in invasive urothelial bladder carcinoma. miR-34a was transfected into bladder cancer cell lines 253J and J82. The miR-34a expression levels in tissues and cells were detected by using qRT-PCR. The Notch1 expression was detected by qRT-PCR and Western blotting. Cell migratory and invasive abilities were measured by Transwell chamber assay. Bioinformatics and luciferase assay were performed to predict and analyze the binding sites between miRNA-34a and Notch1. It was found that there was aberrant expression of miR-34a in bladder cancer tissues. Moreover, we revealed that ectopic expression of miR-34a suppressed cell migration and invasion, while forced expression of Notch1 increased cell migratory and invasive abilities. Finally, we observed that miR-34a transfection significantly down-regulated luciferase activity and reduced the mRNA and protein levels of Notch1. Our study concluded that microRNA-34a antagonizes Notch1 and inhibits cell migration and invasion of bladder cancer cells, which indicates the tumor-suppressive function of microRNA-34a in bladder cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011,61(2):69–90

    Article  PubMed  Google Scholar 

  2. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet, 2008,9(2):102–114

    Article  PubMed  CAS  Google Scholar 

  3. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science, 2004,304(5670): 594–596

    Article  PubMed  CAS  Google Scholar 

  4. Zhang Y, Chao T, Li R, et al. MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med (Berl), 2009,87(1):43–51

    Article  CAS  Google Scholar 

  5. Deng S, Calin GA, Croce CM, et al. Mechanisms of microRNA deregulation in human cancer. Cell Cycle, 2008,7(17):2643–2646

    Article  PubMed  CAS  Google Scholar 

  6. Kong F, Sun C, Wang Z, et al. miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J Huazhong Univ Sci Technol [Med Sci], 2011,31(4):543–549

    Article  CAS  Google Scholar 

  7. Mauviel A. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem, 1993,53(4):288–295

    Article  PubMed  CAS  Google Scholar 

  8. Sporn MB. The war on cancer. Lancet, 1996,347(9012):1377–1381

    Article  PubMed  CAS  Google Scholar 

  9. Lin F, Wang X, Jie Z, et al. Inhibitory effects of miR-146b-5p on cell migration and invasion of pancreatic cancer by targeting MMP16. J Huazhong Univ Sci Technol [Med Sci], 2011,31(4):509–514

    Article  CAS  Google Scholar 

  10. Crawford M, Brawner E, Batte K, et al. MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun, 2008,373(4): 607–612

    Article  PubMed  CAS  Google Scholar 

  11. Li Y, Guessous F, Zhang Y, et al. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res, 2009,69(19):7569–7576

    Article  PubMed  CAS  Google Scholar 

  12. Liu C, Kelnar K, Liu B, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med, 2011,17(2):211–215

    Article  PubMed  CAS  Google Scholar 

  13. Li N, Fu H, Tie Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett, 2009,275(1):44–53

    Article  PubMed  CAS  Google Scholar 

  14. Raver-Shapira N, Marciano E, Meiri E, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell, 2007,26(5):731–743

    Article  PubMed  CAS  Google Scholar 

  15. Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene, 2007,26(34):5017–5022

    Article  PubMed  CAS  Google Scholar 

  16. Miele L, Miao H, Nickoloff BJ. NOTCH signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets, 2006,6(4):313–323

    Article  PubMed  CAS  Google Scholar 

  17. Bolos V, Grego-Bessa J, de la Pompa JL. Notch signaling in development and cancer. Endocr Rev, 2007,28(3): 339–363

    Article  PubMed  CAS  Google Scholar 

  18. Ai X, Zhang XP, Wu Z, et al. Effect of silencing Notch1 on proliferation of bladder cancer cell line T24. J Shandong Univ-Health Sci (Chinese), 2009,47(9):53–57

    CAS  Google Scholar 

  19. Bin Hafeez B, Adhami VM, Asim M, et al. Targeted knockdown of Notch1 inhibits invasion of human prostate cancer cells concomitant with inhibition of matrix metalloproteinase-9 and urokinase plasminogen activator. Clin Cancer Res, 2009,15(2):452–459

    Article  PubMed  CAS  Google Scholar 

  20. Wang Z, Banerjee S, Li Y, et al. Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res, 2006,66(5):2778–2784

    Article  PubMed  CAS  Google Scholar 

  21. Chigurupati S, Venkataraman R, Barrera D, et al. Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness. Cancer Res, 2010,70(1):418–427

    Article  PubMed  CAS  Google Scholar 

  22. Wang J, Fu L, Gu F, et al. Notch1 is involved in migration and invasion of human breast cancer cells. Oncol Rep, 2011,26(5):1295–1303

    PubMed  CAS  Google Scholar 

  23. Pang RT, Leung CO, Ye TM, et al. MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis, 2010,31(6):1037–1044

    Article  PubMed  CAS  Google Scholar 

  24. Shi TP, Xu H, Wei JF, et al. Association of low expression of notch-1 and jagged-1 in human papillary bladder cancer and shorter survival. J Urol, 2008,180(1):361–366

    Article  PubMed  CAS  Google Scholar 

  25. Hu Z, Ai Q, Xu H, et al. Fibulin-5 is down-regulated in urothelial carcinoma of bladder and inhibits growth and invasion of human bladder cancer cell line 5637. Urol Oncol, 2011,29(4):430–435

    Article  PubMed  CAS  Google Scholar 

  26. Babashah S, Soleimani M. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer, 2011,47(87):1127–1137

    Article  PubMed  CAS  Google Scholar 

  27. Heijmans BT, Boer JM, Suchiman HE, et al. A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res, 2003,63(6):1249–1253

    PubMed  CAS  Google Scholar 

  28. Matsumoto H, Matsuyama H, Fukunaga K, et al. Allelic imbalance at 1p36 may predict prognosis of chemoradiation therapy for bladder preservation in patients with invasive bladder cancer. Br J Cancer, 2004,91(6):1025–1031

    PubMed  CAS  Google Scholar 

  29. Vinall RL, Zripoll A, Wang S, et al. MiR-34a chemo-sensitizes bladder cancer cells to cisplatin treatment regardless of P53-Rb pathway status. Int J Cancer, 2011,130(11):2526–2538

    Article  PubMed  Google Scholar 

  30. Gaur A, Jewell DA, Liang Y, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res, 2007,67(6):2456–2468

    Article  PubMed  CAS  Google Scholar 

  31. Yan D, Zhou X, Chen X, et al. MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci, 2009,50(4):1559–1565

    Article  PubMed  Google Scholar 

  32. Potapova IA, Gaudette GR, Brink PR, et al. Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro. Stem Cells, 2007,25(7):1761–1768

    Article  PubMed  CAS  Google Scholar 

  33. Balint K, Xiao M, Pinnix CC, et al. Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. J Clin Invest, 2005,115(11):3166–3176

    Article  PubMed  CAS  Google Scholar 

  34. Willert K, Nusse R. Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev, 1998,8(1):95–102

    Article  PubMed  CAS  Google Scholar 

  35. Liu H, Chen A, Guo F, et al. Influence of osteopontin short hairpin RNA on the proliferation and invasion of human renal cancer cells. J Huazhong Univ Sci Technol [Med Sci], 2010,30(1):61–68

    Article  CAS  Google Scholar 

  36. Delbosc S, Glorian M, Le Port AS, et al. The benefit of docosahexanoic acid on the migration of vascular smooth muscle cells is partially dependent on Notch regulation of MMP-2/-9. Am J Pathol, 2008,172(5):1430–1440

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Chinese PLA General Hospital, Beijing, 100853, China

    Chao Zhang  (张 超), Mingyang Zhu  (朱鸣阳), Xin Ma  (马 鑫), Taoping Shi  (史涛坪), Hongzhao Li  (李宏召), Baojun Wang  (王保军) & Xu Zhang  (张 旭)

  2. Nankai University, Tianjin, 300071, China

    Chao Zhang  (张 超)

  3. Department of Urology, Air Force General Hospital of PLA, Beijing, 1000853, China

    Zhiyong Yao  (姚志勇)

  4. Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China

    Jinzhi Ouyang  (欧阳金芝)

Authors
  1. Chao Zhang  (张 超)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhiyong Yao  (姚志勇)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mingyang Zhu  (朱鸣阳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Ma  (马 鑫)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Taoping Shi  (史涛坪)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongzhao Li  (李宏召)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baojun Wang  (王保军)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jinzhi Ouyang  (欧阳金芝)
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xu Zhang  (张 旭)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xu Zhang  (张 旭).

Additional information

This project was supported by a grant from the National Natural Science Foundation of China (No. 30972982).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, C., Yao, Z., Zhu, M. et al. Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting notch1. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 32, 375–382 (2012). https://doi.org/10.1007/s11596-012-0065-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-012-0065-z

Key words

Search

Navigation