Skip to main content

Advertisement

SpringerLink
Log in

MiR-26a inhibits prostate cancer progression by repression of Wnt5a

  • Research Article
  • Published:
Tumor Biology

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are involved in different biological processes by suppressing target gene expression. miRNA microarray analysis revealed a significant decrease of miR-26a in prostate cancer tissues versus their normal counterparts, but the role of miR-26a is needed to investigate. In the present study, we found that miR-26a expression was lower in prostate cancer tissues compared with their normal controls, so did the prostate cancer cells. Next, by lentivirus-mediated gain-of-function studies, it was showed that stable miR-26a inhibited cell proliferation, metastasis, and epithelial mesenchymal transition and induced G1 phase arrest in prostate cancer. It was predicted that Wnt5a was a potential target gene of miR-26a by bioinformatics analysis. Then, luciferase assay and Western blot analysis identified that Wnt5a was a new direct target gene of miR-26a and miR-26a inhibited prostate cancer progression via Wnt5a. Altogether, the findings suggested that miR-26a may function as a tumor suppressor in prostate cancer by targeting Wnt5a.

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
Fig. 5

Similar content being viewed by others

References

  1. Roehrborn CG, Black LK. The economic burden of prostate cancer. BJU Int. 2011;108:806–13.

    Article  PubMed  Google Scholar 

  2. De Marzo AM, DeWeese TL, Platz EA, Meeker AK, Nakayama M, Epstein JI, et al. Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment. J Cell Biochem. 2004;91:459–77.

    Article  PubMed  Google Scholar 

  3. Isaacs WB, Bova GS, Morton RA, Bussemakers MJ, Brooks JD. Molecular biology of prostate cancer progression. Cancer Surv. 1995;23:19–32.

    CAS  PubMed  Google Scholar 

  4. Kartha RV, Subramanian S. Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet. 2014;5:8. eCollection.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Banno K, Iida M, Yanokura M, Kisu I, Iwata T, Tominaga E, et al. MicroRNA in cervical cancer: oncomirs and tumor suppressor miRs in diagnosis and treatment. ScientificWorldJournal. 2014;2014:178075.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Musiyenko A, Bitko V, Barik S. Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells. J Mol Med (Berl). 2008;86:313–22.

    Article  CAS  Google Scholar 

  7. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 2008;27:4373–9.

    Article  CAS  PubMed  Google Scholar 

  8. Li T, Li D, Sha J, Sun P, Huang Y. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 2009;383:280–5.

    Article  CAS  PubMed  Google Scholar 

  9. Ozen M, Creighton CJ, Ozdemir M, Ittmann M. Widespread deregulation of microRNA expression in human prostate cancer. Oncogene. 2008;27:1788–93.

    Article  CAS  PubMed  Google Scholar 

  10. Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science. 2008;322:1695–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rink C, Khanna S. MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics. 2011;43:521–8.

    Article  CAS  PubMed  Google Scholar 

  12. Song H, Liu Y, Pan J, Zhao ST. Expression profile analysis reveals putative prostate cancer-related microRNAs. Genet Mol Res. 2013;12:4934–43.

    Article  CAS  PubMed  Google Scholar 

  13. Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Müller SC, Ellinger J. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 2011;77:1265.e9–16.

    Article  Google Scholar 

  14. Erdmann K, Kaulke K, Thomae C, Huebner D, Sergon M, Froehner M, et al. Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs. BMC Cancer. 2014;14:82.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kuser-Abali G, Alptekin A, Cinar B. Overexpression of MYC and EZH2 cooperates to epigenetically silence MST1 expression. Epigenetics. 2014;9:634–43.

  16. Börno ST, Fischer A, Kerick M, Fälth M, Laible M, Brase JC, et al. Genome-wide DNA methylation events in TMPRSS2-ERG fusion-negative prostate cancers implicate an EZH2-dependent mechanism with miR-26a hypermethylation. Cancer Discov. 2012;2:1024–35.

    Article  PubMed  Google Scholar 

  17. Koh CM, Iwata T, Zheng Q, Bethel C, Yegnasubramanian S, De Marzo AM. Myc enforces overexpression of EZH2 in early prostatic neoplasia via transcriptional and post-transcriptional mechanisms. Oncotarget. 2011;2:669–83.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fu X, Meng Z, Liang W, Tian Y, Wang X, Han W, et al. miR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis. Oncogene. 2013. doi:10.1038/onc.2013.385

  19. Fu X, Meng Z, Liang W, Tian Y, Wang X, Han W, et al. Four microRNAs promote prostate cell proliferation with regulation of PTEN and its downstream signals in vitro. PLoS One. 2013;8:e75885.

    Article  Google Scholar 

  20. Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 2013;27:2192–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Franco-Chuaire ML, Magda Carolina SC, Chuaire-Noack L. Epithelial-mesenchymal transition (EMT): principles and clinical impact in cancer therapy. Investig Clin. 2013;54:186–205.

    Google Scholar 

  22. Schindeler A, Kolind M, Little DG. Cellular transitions and tissue engineering. Cell Reprogram. 2013;15:101–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Lamouille S, Subramanyam D, Blelloch R, Derynck R. Regulation of epithelial-mesenchymal and mesenchymal-epithelial transitions by microRNAs. Curr Opin Cell Biol. 2013;25:200–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kikuchi A, Yamamoto H, Sato A, Matsumoto S. Wnt5a: its signalling, functions and implication in diseases. Acta Physiol (Oxf). 2012;204:17–33.

    Article  CAS  Google Scholar 

  25. Nishita M, Enomoto M, Yamagata K, Minami Y. Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells. Trends Cell Biol. 2010;20:346–54.

    Article  CAS  PubMed  Google Scholar 

  26. McDonald SL, Silver A. The opposing roles of Wnt-5a in cancer. Br J Cancer. 2009;101:209–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Katoh M. WNT signaling in stem cell biology and regenerative medicine. Curr Drug Targets. 2008;9:565–70.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511447, China

    Shijia Zhao, Xuexiong Lian, Yupeng Feng, Feng Li & Li Li

  2. Department of Urology, Microsurgery Center, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China

    Xiangdong Ye

  3. Department of Emergency, Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511447, China

    Lei Xiao

Authors
  1. Shijia Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiangdong Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuexiong Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yupeng Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Feng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shijia Zhao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, S., Ye, X., Xiao, L. et al. MiR-26a inhibits prostate cancer progression by repression of Wnt5a. Tumor Biol. 35, 9725–9733 (2014). https://doi.org/10.1007/s13277-014-2206-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2206-4

Keywords

Search

Navigation