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Tumor Biology

, Volume 37, Issue 12, pp 16295–16304 | Cite as

MicroRNA-92 promotes invasion and chemoresistance by targeting GSK3β and activating Wnt signaling in bladder cancer cells

Original Article

Abstract

miR-92 has been reported to be upregulated in several human cancers. Until now, its expression pattern and biological roles in human bladder cancer still remains unexplored. The present study aims to clarify its expression, function, and potential molecular mechanisms in bladder cancer. Using real-time PCR, we found that miR-92 was upregulated in bladder cancer tissues compared with normal bladder tissues. We transfected miR-92 mimic and inhibitor in T24 and 5637 bladder cancer cells separately. We found that miR-92 mimic promoted T24 proliferation and invasion, with increased expression of cyclin D1, c-myc, and MMP7 at both mRNA and protein levels. Further investigation found that miR-92 could also promote epithelial-mesenchymal transition by downregulating E-cadherin protein and upregulating vimentin. In addition, miR-92 mimic also promoted activation of Wnt signaling. Meanwhile, miR-92 inhibitor displayed the opposite effects in 5637 cell line. By use of bioinformatic prediction software and luciferase reporter assay, we discovered that GSK3β acted as a direct target of miR-92. Additionally, GSK3β siRNA abrogated the effects of miR-92 mimic on cyclin D1 and MMP7. Moreover, we observed a negative correlation between GSK3β and miR-92 in bladder cancer tissues. In conclusion, our study demonstrated that upregulation of miR-92 is closely related with malignant progression of bladder cancer and miR-92 promotes proliferation, invasion, and Wnt/c-myc/MMP7 signaling by targeting GSK3β.

Keywords

Bladder cancer miR-92 GSK3β Proliferation Invasion 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81260374, 81460384); Yunnan Provincial Department of Education Fund (No. 2014Z072); Joint Project of Science and Technology, Department of Yunnan and Kunming Medical University (Nos. 2014FA015, 2014FZ031); Project of Yunnan Provincial Health Department (No. 2014NS081); and Project of Yunnan Provincial Science and Technology (No. 2015FB196).

Compliance with ethical standards

This study was conducted with the approval of the ethics committee of Kunming Medical University. Written informed consent was obtained from all patients and all clinical investigation has been conducted.

Conflicts of interests

None.

Supplementary material

13277_2016_5460_Fig8_ESM.gif (84 kb)
Supplement Figure 1

Prediction results from miRNAorg. miRNAorg showed that GSK3β was a potential target for miR-92. (GIF 83 kb)

13277_2016_5460_MOESM1_ESM.tif (22 kb)
High resolution image (TIFF 22 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Haifeng Wang
    • 1
  • Changxing Ke
    • 1
  • Xingyong Ma
    • 1
  • Qinghua Zhao
    • 1
  • Mingying Yang
    • 1
  • Wei Zhang
    • 2
  • Jiansong Wang
    • 1
  1. 1.Department of UrologyThe Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of UrologyKunmingChina
  2. 2.Department of UrologyAffiliated Hospital of Hebei UniversityBaodingChina

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