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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition

Authors: Ming Sun, Xiang-Hua Liu, Ke-Ming Wang, Feng-qi Nie, Rong Kong, Jin-song Yang, Rui Xia, Tong-Peng Xu, Fei-Yan Jin, Zhi-Jun Liu, Jin-fei Chen, Er-Bao Zhang, Wei De, Zhao-Xia Wang

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its’ molecular mechanisms controlling cancer cell migration and metastasis are unclear.

Methods

Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry.

Results

BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression.

Conclusion

We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.
Appendix
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Metadata
Title
Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition
Authors
Ming Sun
Xiang-Hua Liu
Ke-Ming Wang
Feng-qi Nie
Rong Kong
Jin-song Yang
Rui Xia
Tong-Peng Xu
Fei-Yan Jin
Zhi-Jun Liu
Jin-fei Chen
Er-Bao Zhang
Wei De
Zhao-Xia Wang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-68

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