Tumor Biology

, Volume 37, Issue 2, pp 1461–1469 | Cite as

Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway

Review

Abstract

The aberrant expression of MEG3 has been found in some types of cancers; however, little is known concerning the function of MEG3 in retinoblastoma. To elucidate the roles of MEG3 in retinoblastoma, MEG3 expression was quantified in 63 retinoblastoma samples and corresponding nontumor tissues in this work. Moreover, retinoblastoma cell lines were transfected with pcDNA3.1-MEG3 or si-MEG3, after which proliferation, apoptosis, and expression of β-catenin were assayed. TOP-Flash reporter assay was also used to investigate the activity of the Wnt/β-catenin pathway. The results showed that MEG3 was downregulated in retinoblastoma tissues, and the level of MEG3 was negatively associated with IIRC stages and nodal or distant metastasis. More importantly, Kaplan-Meier survival analysis demonstrated that patients with low MEG3 expression had poorer survival and multivariate Cox regression analysis revealed that MEG3 was an independent prognostic factor in retinoblastoma patients. We also observed that MEG3 expression can be modulated by DNA methylation by using 5-aza-CdR treatment. In addition, overexpression of MEG3 suppressed proliferation, promoted apoptosis, and influences the activity of the Wnt/β-catenin pathway in retinoblastoma cell lines. Furthermore, we found that Wnt/β-catenin pathway activator rescued the anticancer effect of MEG3 in retinoblastoma. In conclusion, our study for the first time demonstrated that MEG3 was a tumor suppressor by negatively regulating the activity of the Wnt/β-catenin pathway in the progression of retinoblastoma and might serve as a prognostic biomarker and molecular therapeutic target.

Keywords

Retinoblastoma Long noncoding RNA MEG3 Wnt/β-catenin pathway Prognosis Proliferation 

Notes

Acknowledgments

This project was supported by the Health and Family Commission of Shenzhen Municipality Foundation (grant no. 201507010).

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2015_4564_MOESM1_ESM.pdf (13 kb)
Online Resource 1 (PDF 12 kb)
13277_2015_4564_MOESM2_ESM.pdf (17 kb)
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13277_2015_4564_MOESM3_ESM.pdf (115 kb)
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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of OphthalmologyZhujiang Hospital of Southern Medical UniversityGuangzhouPeople’s Republic of China
  2. 2.Department of OphthalmologyShenzhen People’s HospitalShenzhenPeople’s Republic of China

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