Tumor Biology

, Volume 35, Issue 9, pp 8565–8572 | Cite as

miR-122/Wnt/β-catenin regulatory circuitry sustains glioma progression

  • Guangzhi Wang
  • Yan Zhao
  • Yongri Zheng
Research Article


Malignant glioma is the most common type of human intracranial cancer and has poor prognosis due to its high recurrence and invasiveness. However, the molecular mechanisms underlying its malignant phenotypes have still not been completely explored yet. miR-122 has been well documented to act as a tumor suppressor for hepatocellular carcinoma and breast cancer, but the implication of miR-122 in the progression of glioma is not clear yet. In this study, we found that miR-122 was underexpressed in glioma specimens and glioma cell lines, compared with normal brain tissues and cell lines. The expression of miR-122 levels is inversely correlated with the survival of patients after surgery. Overexpression of miR-122 by an adenoviral vector suppressed the proliferation and colony formation of glioma cells. The in vivo tumorigenicity of U-87 MG cells was also greatly compromised by restoring miR-122. miR-122 suppressed the activation of Wnt/β-catenin pathway in glioma cells. Interestingly, Wnt/β-catenin signaling conversely reduced the expression of miR-122 in glioma cells, maybe in a hepatocyte nuclear factor (HNF)-dependent mechanism. Taken together, we revealed that there is a miR-122/Wnt/β-catenin regulatory circuitry existing in glioma cells that contributes to glioma progression.


Glioma miR-122 Wnt/β-catenin Adenovirus 


Conflicts of interest


Supplementary material

13277_2014_2089_MOESM1_ESM.pptx (71 kb)
Supplementary Fig. 1 The survival of patients with low or high level of miR-122 was subjected to Kaplan-Meier survival analysis. 21 patients with the highest miR-122 levels are defined as high miR-122 group, while 21 patients with the lowest miR-122 levels as low miR-122 group. (PPTX 71 kb)
13277_2014_2089_MOESM2_ESM.pptx (45 kb)
Supplementary Fig. 2 Apoptosis of U-87 MG and U-251 MG cells was determined at the indicated time points by cytometrical analysis when Ad-miR122 or Ad-EGFP (10 MOI) was used. The data were shown as means ± SD of three independent experiments. (PPTX 44 kb)
13277_2014_2089_MOESM3_ESM.pptx (57 kb)
Supplementary Fig. 3 miR-122 suppressed the expression of WNT1 by binding its 3UTR. U-87 MG cells were transfected with psiCheck2, psiCheck2-WNT1-3UTR and psiCheck2-WNT1-3UTR-mut. After 12 h, the cells were infected with Ad-miR122 or Ad-EGFP (10 MOI) for 48 h. Relative luciferase expression was assessed and shown as means ± SD of three independent experiments. (PPTX 56 kb)
13277_2014_2089_MOESM4_ESM.pptx (1.8 mb)
Supplementary Fig. 4 Nuclear accumulation of β-catenin was diminished in U-87 MG and U-251 MG cells transfected with Ad-miR122 or Ad-EGFP (10 MOI) for 48 h. (PPTX 1878 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of NeurosurgeryHarbin Medical University Second Affiliated HospitalHarbinChina

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