MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration.
MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration.
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DOI：
10.1002/ijc.25939
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Weiss, Glen J.
中科院分区：
文献类型：
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作者：
Arora, Shilpi;Ranade, Aarati R.;Tran, Nhan L.;Nasser, Sara;Sridhar, Shravan;Korn, Ronald L.;Ross, Julianna T. D.;Dhruv, Harshil;Foss, Kristen M.;Sibenaller, Zita;Ryken, Timothy;Gotway, Michael B.;Kim, Seungchan;Weiss, Glen J.
脑转移（BM）可影响约25%的非小细胞肺癌（NSCLC）患者的一生。描述将发展为BM的患者的努力令人失望。microRNA（miRNAs）调节靶mRNA的表达。miRNAs在调节多种靶点和多种途径中发挥作用，这使其成为疾病早期检测、风险评估和预后的有力工具。我们研究了可能作为生物标志物的miRNA，以区分有和无BM的NSCLC患者。对来自7名BM（BM+）和6名无BM（BM-）的临床匹配NSCLC患者的样本进行miRNA微阵列分析。通过t检验和进一步的qRT-PCR验证，证实了8种miRNAs的显著差异表达。其中，miR-328和miR-330- 3 p的表达能够正确分类BM+与BM-患者。该分类器用于验证队列（n=15），并正确分类了12/15例患者。比较A549亲本和稳定转染以过表达miR-328（A549-328）的A549细胞的基因表达分析鉴定了几个显著差异表达的基因。PRKCA是A549-328细胞中过表达的基因之一。此外，与A549细胞相比，A549-328细胞具有显著增加的细胞迁移，其在PRKCA敲低后显著降低。总之，miR-328在赋予NSCLC细胞迁移潜力方面具有作用，部分通过PRKCA起作用，并且在其他独立队列中得到进一步证实，这些miRNA可被纳入临床治疗决策中，以将具有较高BM发展风险的NSCLC患者分层。
Brain metastasis (BM) can affect ~25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. microRNAs (miRNAs) regulate the expression of target mRNAs. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment, and prognosis. We investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from seven patients with BM (BM+) and six without BM (BM−). Using t-test and further qRT-PCR validation, eight miRNAs were confirmed to be significantly differentially-expressed. Of these, expression of miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM− patients. This classifier was used on a validation cohort (n=15) and it correctly classified 12/15 patients. Gene expression analysis comparing A549 parental and A549 cells stably transfected to over-express miR-328 (A549–328) identified several significantly differentially-expressed genes. PRKCA was one of the genes over-expressed in A549–328 cells. Additionally, A549–328 cells had significantly increased cell migration compared to A549 cells, which was significantly reduced upon PRKCA knockdown. In summary, miR-328 has a role in conferring migratory potential to NSCLC cells working in part through PRKCA and with further corroboration in additional independent cohorts, these miRNAs may be incorporated into clinical treatment decision making to stratify NSCLC patients at higher risk for developing BM.
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影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1158/1078-0432.ccr-09-1736
发表时间：
2010-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Landi MT;Zhao Y;Rotunno M;Koshiol J;Liu H;Bergen AW;Rubagotti M;Goldstein AM;Linnoila I;Marincola FM;Tucker MA;Bertazzi PA;Pesatori AC;Caporaso NE;McShane LM;Wang E
通讯作者：
Wang E
DOI：
10.1073/pnas.0802682105
发表时间：
2008-05-20
影响因子：
11.1
作者：
Jazdzewski, Krystian;Murray, Elizabeth L.;de la Chapelle, Albert
通讯作者：
de la Chapelle, Albert
影响因子：
11.2
作者：
Chin LJ;Ratner E;Leng S;Zhai R;Nallur S;Babar I;Muller RU;Straka E;Su L;Burki EA;Crowell RE;Patel R;Kulkarni T;Homer R;Zelterman D;Kidd KK;Zhu Y;Christiani DC;Belinsky SA;Slack FJ;Weidhaas JB
通讯作者：
Weidhaas JB