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Tumor Biology

, Volume 37, Issue 3, pp 3051–3057 | Cite as

ZNRF3 contributes to the growth of lung carcinoma via inhibiting Wnt/β-catenin pathway and is regulated by miR-93

  • Jichan Shi
  • Xiangao Jiang
  • Zhijie Yu
  • Guiqing He
  • Hongye Ning
  • Zhengxing Wu
  • Yuwei Cai
  • Hehe Yu
  • Aiqiong Chen
Original Article

Abstract

Lung carcinoma is the most common cancer with increasing morbidity, inefficient therapeutic modality, and poor prognosis, due to the lack of understanding of its related molecular mechanism. ZNRF3 is a newly identified negative regulator of Wnt signaling. In this study, we found that ZNRF3 level is reduced in lung carcinoma compared with normal lung tissue and its expression level is positively correlated with the survival of lung cancer patients. Restoration of ZNRF3 suppressed the proliferation and cell cycle progression of lung cancer cell lines. Suppression of ZNRF3 expression in normal lung cells increased the proliferation rates. In an animal model, ZNRF3 was shown to suppress the growth of lung cancer xenografts. ZNRF3 was shown to negatively regulate the activation of Wnt signaling in lung cancerous and normal cells. Further studies revealed that ZNRF3 is a target of miR-93, an oncogenic microRNA (miRNA) for lung cancer progression. Collectively, we found that miR-93/ZNRF3/Wnt/β-catenin regulatory network contributes to the growth of lung carcinoma. Targeting this pathway may be a promising strategy for lung cancer therapy.

Keywords

Lung carcinoma miR-93 Wnt/β-catenin ZNRF3 

Notes

Conflicts of interest

None

Supplementary material

13277_2015_3949_MOESM1_ESM.pptx (50 kb)
SFig. 1 ZNRF3 affects the formation of colony derived from lung carcinoma and normal lung cells. (A) A549 cells were infected with Ad-EGFP (10 MOI) or Ad-ZNRF3 (10 MOI), and 7 d later, colony formation assay was performed to detect the effect of ZNRF3 on their colony formation ability. (B) MRC-5 cells were transfected with control (10 ng/mL) or ZNRF3 siRNA (10 ng/mL), and 7 d later, colony formation assay was performed to detect the effect of ZNRF3 on their colony formation ability. (PPTX 50 kb)
13277_2015_3949_MOESM2_ESM.pptx (55 kb)
SFig. 2 miR-93 has no influence on NF-kB pathway. (A) A549 cells were transfected with miR-93 inhibitor (30 nM) or control molecules (30 nM), and 48 h later, NF-kB responsive luciferase construct was used to detect the activation of NF-kB signaling. (B) MRC-5 cells were transfected with miR-93 mimics (30 nM) or control molecules (30 nM), and 48 h later, NF-kB responsive luciferase construct was used to detect the activation of NF-kB signaling. (PPTX 55 kb)
13277_2015_3949_MOESM3_ESM.pptx (55 kb)
SFig. 3 miR-93 has no influence on Wnt pathway. (A) A549 cells were transfected with miR-93 inhibitor (30 nM) or control molecules (30 nM), and 48 h later, TCF/LCF responsive luciferase construct was used to detect the activation of Wnt signaling. (B) MRC-5 cells were transfected with miR-93 mimics (30 nM) or control molecules (30 nM), and 48 h later, TCF/LCF responsive luciferase construct was used to detect the activation of Wnt signaling. (PPTX 55 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jichan Shi
    • 1
  • Xiangao Jiang
    • 1
  • Zhijie Yu
    • 2
  • Guiqing He
    • 1
  • Hongye Ning
    • 1
  • Zhengxing Wu
    • 1
  • Yuwei Cai
    • 1
  • Hehe Yu
    • 1
  • Aiqiong Chen
    • 1
  1. 1.Department of Infectious DiseasesWenzhou Central HospitalWenzhouChina
  2. 2.Department of Scientific Research CenterThe First Hospital Affiliated to Wenzhou Medical CollegeWenzhouChina

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