Tumor Biology

, Volume 35, Issue 10, pp 9725–9733 | Cite as

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

  • Shijia Zhao
  • Xiangdong Ye
  • Lei Xiao
  • Xuexiong Lian
  • Yupeng Feng
  • Feng Li
  • Li Li
Research Article


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.


Prostate cancer Metastasis Wnt5a miR-26a 


  1. 1.
    Roehrborn CG, Black LK. The economic burden of prostate cancer. BJU Int. 2011;108:806–13.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 3.
    Isaacs WB, Bova GS, Morton RA, Bussemakers MJ, Brooks JD. Molecular biology of prostate cancer progression. Cancer Surv. 1995;23:19–32.PubMedGoogle Scholar
  4. 4.
    Kartha RV, Subramanian S. Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet. 2014;5:8. eCollection.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 9.
    Ozen M, Creighton CJ, Ozdemir M, Ittmann M. Widespread deregulation of microRNA expression in human prostate cancer. Oncogene. 2008;27:1788–93.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Rink C, Khanna S. MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics. 2011;43:521–8.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kuser-Abali G, Alptekin A, Cinar B. Overexpression of MYC and EZH2 cooperates to epigenetically silence MST1 expression. Epigenetics. 2014;9:634–43.Google Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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. 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.CrossRefGoogle Scholar
  20. 20.
    Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 2013;27:2192–206.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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. 22.
    Schindeler A, Kolind M, Little DG. Cellular transitions and tissue engineering. Cell Reprogram. 2013;15:101–6.PubMedPubMedCentralGoogle Scholar
  23. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kikuchi A, Yamamoto H, Sato A, Matsumoto S. Wnt5a: its signalling, functions and implication in diseases. Acta Physiol (Oxf). 2012;204:17–33.CrossRefGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 26.
    McDonald SL, Silver A. The opposing roles of Wnt-5a in cancer. Br J Cancer. 2009;101:209–14.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Katoh M. WNT signaling in stem cell biology and regenerative medicine. Curr Drug Targets. 2008;9:565–70.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shijia Zhao
    • 1
  • Xiangdong Ye
    • 2
  • Lei Xiao
    • 3
  • Xuexiong Lian
    • 1
  • Yupeng Feng
    • 1
  • Feng Li
    • 1
  • Li Li
    • 1
  1. 1.Department of UrologyFourth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
  2. 2.Department of Urology, Microsurgery CenterFirst Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
  3. 3.Department of EmergencyFourth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

Personalised recommendations