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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. 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.

SUBMITTER: Sun M

PROVIDER: S-EPMC3998010 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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.

Sun Ming M Liu Xiang-Hua XH Wang Ke-Ming KM Nie Feng-qi FQ Kong Rong R Yang Jin-song JS Xia Rui R Xu Tong-Peng TP Jin Fei-Yan FY Liu Zhi-Jun ZJ Chen Jin-fei JF Zhang Er-Bao EB De Wei W Wang Zhao-Xia ZX

Molecular cancer 20140321

<h4>Background</h4>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 migrati ...[more]

PMID: 24655544

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Project description:BackgroundRecent evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in the regulation of cellular processes and are found to be dysregulated in a variety of cancers. LINC00261 is an lncRNA that is aberrantly expressed in gastric cancer (GC). The clinical role of LINC00261 in GC and molecular mechanisms remains to be found.MethodsReal-time polymerase chain reaction (PCR) was used to examine LINC00261 expression in GC cell lines/tissues compared with normal epithelial cells/adjacent non-tumorous tissues. Gain and loss of function approaches were used to investigate the biological role of LINC00261 in GC cells. The effects of LINC00261 on cell viability were evaluated by MTT and colony formation assays. Wound healing assay, cell migration and invasion assays, and nude mice were used to examine the effects of LINC00261 on tumor cell metastasis in vitro and in vivo. Protein levels of LINC00261 targets were determined by western blot and immunohistochemistry.ResultsLINC00261 was downregulated in GC cell lines and cancerous tissues, as compared with normal gastric epithelial cells and adjacent noncancerous tissue samples. Low LINC00261 expression was correlated with deeper tumor invasion (P < 0.001), higher tumor stage (P = 0.013), and lymphatic metastasis (P = 0.006). Univariate and multivariate analyses indicated that low LINC00261 expression predicted poor prognosis. Ectopic expression of LINC00261 impaired cell migration and invasion, leading to the inhibition of metastasis in vitro and in vivo. Knockdown of LINC00261 expression promoted cell migration and invasion in vitro. Overexpression of LINC00261 was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin, and Vimentin expression.ConclusionsLow expression of the lncRNA LINC00261 occurs in GC and is associated with poor prognosis. LINC00261 suppresses GC metastasis by regulating EMT. Thus, LINC00261 plays an important role in the progression and metastasis of GC.

Dataset Information

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.

Publications

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.

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