Skip to main content

Advertisement

SpringerLink
Log in

miR-335 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells through direct suppression of BCL-W

  • Research Article
  • Published:
Tumor Biology

Abstract

Increasing evidence has demonstrated that small non-coding microRNAs (miRNAs) play important roles in cancer development and progression. Recent studies have shown that microRNA-335 (miR-335) functions as an oncogene or a tumor suppressor in various human cancer types, but its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. In our study, we firstly found that the expression level of miR-335 was significantly downregulated in ccRCC tissues versus corresponding non-tumor tissues and the low expression of miR-335 was significantly associated with lymph node metastasis, larger tumor size, and poor T stage. Then, we found that overexpression of miR-335 significantly suppressed the proliferation and invasion of 786-O and CaKi-1 ccRCC cell lines. We subsequently found that miR-335 could interact with the 3′-untranslated regions (3′UTR) of B-cell CLL/lymphoma 2 like 2 (BCL-W or BCL2L2) messenger RNA (mRNA) and repress its expression. In addition, re-expression of BCL-W (without the 3′UTR) could partially abrogate the miR-335-induced 786-O and CaKi-1 ccRCC cell proliferation and invasion inhibition. Furthermore, we found that expression patterns of miR-335 were inversely correlated with those of BCL-W mRNA in ccRCC tissues. Taken together, these results indicate that miR-335 acts as a novel tumor suppressor to regulate ccRCC cell proliferation and invasion through downregulation of BCL-W expression.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

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

    Article  PubMed  Google Scholar 

  2. Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005;353(23):2477–90.

    Article  CAS  PubMed  Google Scholar 

  3. Park K, Lee JL, Park I, et al. Comparative efficacy of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor as second-line therapy in patients with metastatic renal cell carcinoma after the failure of first-line VEGF TKI. Med Oncol. 2012;29(5):3291–7.

    Article  CAS  PubMed  Google Scholar 

  4. Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 2010;11:252–63.

    Article  CAS  PubMed  Google Scholar 

  5. Khella HW, White NM, Faragalla H, et al. Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses. Tumor Biol. 2012;33:131–40.

    Article  CAS  Google Scholar 

  6. Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128–36.

    Article  CAS  PubMed  Google Scholar 

  7. Kong W, He L, Richards EJ, et al. Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene. 2014;33(6):679–89.

    Article  CAS  PubMed  Google Scholar 

  8. Shu M, Zhou Y, Zhu W, et al. MicroRNA-335 is required for differentiation of malignant glioma cells induced by activation of cAMP/protein kinase A pathway. Mol Pharmacol. 2012;81(3):292–8.

    Article  CAS  PubMed  Google Scholar 

  9. Tavazoie SF, Alarcón C, Oskarsson T, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang F, Zheng Z, Guo J, et al. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119(3):586–93.

    Article  CAS  PubMed  Google Scholar 

  11. Gao Y, Zeng F, Wu JY, et al. MiR-335 inhibits migration of breast cancer cells through targeting oncoprotein c-Met. Tumour Biol. 2014.

  12. Sorrentino A, Liu CG, Addario A, et al. Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol. 2008;111(3):478–86.

    Article  CAS  PubMed  Google Scholar 

  13. Gao L, Yang Y, Xu H, et al. MiR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4. Tumour Biol. 2014;35(8):8309–18.

    Article  CAS  PubMed  Google Scholar 

  14. Wang H, Li M, Zhang R, et al. Effect of miR-335 upregulation on the apoptosis and invasion of lung cancer cell A549 and H1299. Tumour Biol. 2013;34(5):3101–9.

    Article  CAS  PubMed  Google Scholar 

  15. Xiong SW, Lin TX, Xu KW, et al. MicroRNA-335 acts as a candidate tumor suppressor in prostate cancer. Pathol Oncol Res. 2013;19(3):529–37.

    Article  CAS  PubMed  Google Scholar 

  16. Yan Z, Xiong Y, Xu W, et al. Identification of hsa-miR-335 as a prognostic signature in gastric cancer. PLoS One. 2012;7(7):e40037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shu M, Zheng X, Wu S, et al. Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells. Mol Cancer. 2011;10:59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shi L, Jiang D, Sun G, et al. miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas. Neuro-Oncology. 2012;110(2):155–62.

    Article  CAS  Google Scholar 

  19. Ren KM, Bai JX, Wang SN, et al. Identification of potential biomarkers for clear cell renal cell carcinoma based on microRNA-mRNA pathway relationships. J Cancer Res Ther. 2014;10(Suppl):C167–77.

    PubMed  Google Scholar 

  20. Hidaka H, Seki N, Yoshino H, et al. Tumor suppressive microRNA-1285 regulates novel molecular targets: aberrant expression and functional significance in renal cell carcinoma. Oncotarget. 2012;3(1):44–57.

    PubMed  PubMed Central  Google Scholar 

  21. White NM, Bao TT, Grigull J, et al. miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol. 2011;186(3):1077–83.

    Article  CAS  PubMed  Google Scholar 

  22. Shen L, Li J, Xu L, et al. miR-497 induces apoptosis of breast cancer cells by targeting BCL-W. Exp Ther Med. 2012;3(3):475–80.

    CAS  PubMed  Google Scholar 

  23. Cao J, Cai J, Huang D, et al. miR-335 represents an invasion suppressor gene in ovarian cancer by targeting BCL-W. Oncol Rep. 2013;30(2):701–6.

    CAS  PubMed  Google Scholar 

  24. Xu Y, Zhao F, Wang Z, et al. MicroRNA-335 acts as a metastasis suppressor in by targeting BCL-W and specificity protein 1. Oncogene. 2012;31(11):1398–407.

    Article  CAS  PubMed  Google Scholar 

  25. Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  26. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  27. Yates LA, Norbury CJ, Gilbert RJ. The long and short of microRNA. Cell. 2013;153(3):516–9.

    Article  CAS  PubMed  Google Scholar 

  28. Dassow H, Aigner A. MicroRNAs (miRNAs) in colorectal cancer: from aberrant expression towards therapy. Curr Pharm Des. 2013;19(7):1242–52.

    CAS  PubMed  Google Scholar 

  29. Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13(15):1899–911.

    Article  CAS  PubMed  Google Scholar 

  30. Antonsson B. Bax and other pro-apoptotic Bcl-2 family “killer-proteins” and their victim the mitochondrion. Cell Tissue Res. 2001;306(3):347–61.

    Article  CAS  PubMed  Google Scholar 

  31. Uren RT, Dewson G, Chen L, et al. Mitochondrial permeabilization relies on BH3 ligands engaging multiple prosurvival Bcl-2 relatives, not Bak. J Cell Biol. 2007;177(2):277–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bae IH, Yoon SH, Lee SB, et al. Signaling components involved in BCL-W-induced migration of gastric cancer cells. Cancer Lett. 2009;277(1):22–8.

    Article  CAS  PubMed  Google Scholar 

  33. Lee HW, Lee SS, Lee SJ, et al. BCL-W is expressed in a majority of infiltrative gastric adenocarcinomas and suppresses the cancer cell death by blocking stress-activated protein kinase/c-Jun NH2-terminal kinase activation. Cancer Res. 2003;63(5):1093–100.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the General Science Research Program of the Education Department of Liaoning Province in China (No. L2014310).

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Urology, Sheng Jing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Kefeng Wang, Xiaonan Chen, Yunhong Zhan, Xuefeng Liu, Xia Wang & Bin Wu

  2. Department of Pathology, Sheng Jing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Weiguo Jiang

Authors
  1. Kefeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaonan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yunhong Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Weiguo Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuefeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bin Wu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, K., Chen, X., Zhan, Y. et al. miR-335 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells through direct suppression of BCL-W . Tumor Biol. 36, 6875–6882 (2015). https://doi.org/10.1007/s13277-015-3382-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3382-6

Keywords

Search

Navigation