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.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Wang
authors.forename: Feng-qi
authors.initials: FQ
authors.lastname: Nie
authors.forename: Rong
authors.initials: R
authors.lastname: Kong
authors.forename: Jin-song
authors.initials: JS
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.forename: Tong-Peng
authors.initials: TP
authors.lastname: Xu
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Jin
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Jin-fei
authors.initials: JF
authors.lastname: Chen
authors.forename: Er-Bao
authors.initials: EB
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, People's Republic of China. dewei@njmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis* / Q000235:genetics; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D062085:RNA, Long Noncoding; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf