Abstract
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.
Highlights
Recent evidence indicates that long noncoding RNAs play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis
BRAF activated non-coding RNA (BANCR) expression was downregulated and correlated with poor prognosis of non-small cell lung cancer (NSCLC) BANCR expression levels were investigated in 113 paired NSCLC samples and adjacent histologically normal tissues using quantitative polymerase chain reaction assays
BANCR inhibits NSCLC cell viability and induces apoptosis To assess the biological role of BANCR in NSCLC, we investigated the effects of BANCR over-expression on the viability and apoptosis of SPCA1 or A549 cells
Summary
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. One of the most crucial steps in the metastatic cascade is the acquisition of invasive capabilities, including turnover of cell-cell junctions, degradation of the cell matrix, and activation of pathways that control cytoskeletal dynamics in cancer cells. This process is accompanied by multiple changes in gene expression, such as the loss of epithelial markers and a gain in mesenchymal markers [5,6]. Cell and tumor biologists have identified the key role of epithelial-mesenchymal transition (EMT) in cancer cell metastasis, a biological process where epithelial cells lose their polarity and undergo transition into a mesenchymal phenotype [7]
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