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.
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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BRAF激活的非编码RNA的下调与非小细胞肺癌的不良预后相关，并通过影响上皮间质转化促进转移
DOI：
10.1186/1476-4598-13-68
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发表时间：
2014-03-21
期刊：
影响因子：
37.3
通讯作者：
Wang ZX
中科院分区：
文献类型：
--
作者：
Sun M;Liu XH;Wang KM;Nie FQ;Kong R;Yang JS;Xia R;Xu TP;Jin FY;Liu ZJ;Chen JF;Zhang EB;De W;Wang ZX
研究背景最近的研究表明，长链非编码RNA（longnoncodingRNAs，lncRNAs）在细胞分化、增殖和转移等过程中起着重要的调控作用。发现这些lncRNA在多种癌症中失调。BRAF激活的非编码RNA（BANCR）是9号染色体上的693 bp转录本，在黑色素瘤细胞迁移中具有潜在的功能作用。BANCR的临床意义及其控制癌细胞迁移和转移的分子机制尚不清楚。方法采用定量聚合酶链反应（qPCR）方法检测113例非小细胞肺癌（NSCLC）组织和7株NSCLC细胞系中BANCR的表达。使用功能获得和丧失方法来研究BANCR在NSCLC细胞中的生物学作用。MTT法和集落形成实验检测BANCR对细胞活力的影响。Hoechst染色和流式细胞术检测细胞凋亡。采用裸鼠移植瘤模型观察BANCR对肿瘤细胞转移的影响。采用免疫印迹和荧光免疫组化方法检测113例非小细胞肺癌组织中BANCR蛋白的表达水平。此外，BANCR表达降低与NSCLC患者的肿瘤大小、病理分期、转移距离和总生存期缩短相关。BANCR表达降低是NSCLC的独立预后因素。组蛋白去乙酰化参与了NSCLC细胞中BANCR的下调。BANCR的异位表达损害细胞活力和侵袭力，导致体外和体内转移的抑制。然而，BANCR表达的敲低促进了细胞的迁移和侵袭。BANCR的过表达通过调节E-cadherin、N-cadherin和Vimentin的表达在上皮间质转化（EMT）中发挥关键作用。结论我们确定BANCR在NSCLC转移过程中作为EMT的调节因子发挥积极作用，提示BANCR可能是NSCLC预后不良的生物标志物。
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 metastasisin 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 metastasisin vitroandin vivo. However, knockdown of BANCR expression promoted cell migration and invasionin 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.
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影响因子：
8
作者：
Braconi, C.;Kogure, T.;Valeri, N.;Huang, N.;Nuovo, G.;Costinean, S.;Negrini, M.;Miotto, E.;Croce, C. M.;Patel, T.
通讯作者：
Patel, T.
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Gao D;Vahdat LT;Wong S;Chang JC;Mittal V
通讯作者：
Mittal V
DOI：
10.3816/clm.2008.n.021
发表时间：
2008-06-01
期刊：
CLINICAL LYMPHOMA & MYELOMA
影响因子：
--
作者：
Benetatos, Leonidas;Dasoula, Aggeliki;Bourantas, Konstantinos L.
通讯作者：
Bourantas, Konstantinos L.