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

Molecular Cancer

Research

Xiang-Hua Liu¹  Zhi-Jun Liu¹  Rong Kong¹  Wei De¹  Er-Bao Zhang¹  Rui Xia¹  Fei-Yan Jin¹  Ming Sun¹  Tong-Peng Xu²  Feng-qi Nie²  Jin-song Yang³  Jin-fei Chen³  Ke-Ming Wang⁴  Zhao-Xia Wang⁴ 

[1] Department of Biochemistry and Molecular Biology, Nanjing Medical University, 210029, Nanjing, People’s Republic of China;Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China;Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, P. R. China;Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, 210011, Nanjing, Jiangsu, People’s Republic of China;

关键词: A549 Cell;    NSCLC Cell;    Normal Human Bronchial Epithelial Cell;    16HBE Cell;    Advanced Pathological Stage;   

DOI  :  10.1186/1476-4598-13-68

 received in 2013-09-16, accepted in 2014-03-13,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundRecent 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.MethodsExpression 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.ResultsBANCR 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.ConclusionWe 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.

【 授权许可】

Unknown   
© sun et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.