Identifying microRNAs regulating B7-H3 in breast cancer: the clinical impact of microRNA-29c.
Identifying microRNAs regulating B7-H3 in breast cancer: the clinical impact of microRNA-29c.
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DOI：
10.1038/bjc.2014.113
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发表时间：
2014-04-15
影响因子：
8.8
通讯作者：
Leivonen, S-K
中科院分区：
文献类型：
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作者：
Nygren, M. K.;Tekle, C.;Ingebrigtsen, V. A.;Makela, R.;Krohn, M.;Aure, M. R.;Nunes-Xavier, C. E.;Perala, M.;Tramm, T.;Alsner, J.;Overgaard, J.;Nesland, J. M.;Borgen, E.;Borresen-Dale, A-L;Fodstad, O.;Sahlberg, K. K.;Leivonen, S-K
B7-H3是一种免疫调节蛋白，在几种癌症中过表达，通常与转移和预后不良有关。在这里，我们的目的是鉴定调节B7-H3的microRNAs（miRNAs），并评估其在乳腺癌中的潜在预后意义。通过用810个miRNA模拟物的文库筛选两个乳腺癌细胞系并使用蛋白裂解物微阵列定量B7-H3蛋白水平的变化来鉴定靶向B7-H3的microRNA。为了验证，我们使用蛋白质免疫印迹和3′-UTR荧光素酶测定。通过分析两组乳腺癌患者（142例和81例患者）的表达水平是否与预后相关来分析miRNAs的临床意义。我们鉴定了近50种下调B7-H3蛋白水平的miRNA。Western免疫印迹验证了20种最有效的miRNAs的影响。十三种miRNA（miR-214、miR-363*、miR-326、miR-940、miR-29 c、miR-665、miR-34 b *、miR-708、miR-601、miR-124 a、miR-380- 5 p、miR-885- 3 p和miR-593）通过结合其3 '-UTR区域直接靶向B7-H3。最后，miR-29 c的高表达与两个队列中死于乳腺癌的风险显著降低相关。我们鉴定了有效下调B7-H3表达的miRNAs。miR-29 c的表达与乳腺癌患者的生存率相关，表明该miRNA具有肿瘤抑制作用。
B7-H3, an immunoregulatory protein, is overexpressed in several cancers and is often associated with metastasis and poor prognosis. Here, our aim was to identify microRNAs (miRNAs) regulating B7-H3 and assess their potential prognostic implications in breast cancer. MicroRNAs targeting B7-H3 were identified by transfecting two breast cancer cell lines with a library of 810 miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate microarrays. For validations we used western immunoblotting and 3′-UTR luciferase assays. Clinical significance of the miRNAs was assayed by analysing whether their expression levels correlated with outcome in two cohorts of breast cancer patients (142 and 81 patients). We identified nearly 50 miRNAs that downregulated B7-H3 protein levels. Western immunoblotting validated the impact of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and miR-593) targeted B7-H3 directly by binding to its 3′-UTR region. Finally, high expression of miR-29c was associated with a significant reduced risk of dying from breast cancer in both cohorts. We identified miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c correlated with survival in breast cancer patients, suggesting a tumour suppressive role for this miRNA.
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影响因子：
3.7
作者：
Myhre S;Mohammed H;Tramm T;Alsner J;Finak G;Park M;Overgaard J;Børresen-Dale AL;Frigessi A;Sørlie T
通讯作者：
Sørlie T
DOI：
10.1158/1078-0432.ccr-11-2857
发表时间：
2012-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jang JS;Jeon HS;Sun Z;Aubry MC;Tang H;Park CH;Rakhshan F;Schultz DA;Kolbert CP;Lupu R;Park JY;Harris CC;Yang P;Jen J
通讯作者：
Jen J
免疫调节配体的B7家族。
影响因子：
12.3
作者：
Collins, Mary;Ling, Vincent;Carreno, Beatriz M
通讯作者：
Carreno, Beatriz M
影响因子：
5.7
作者：
Liu H;Tekle C;Chen YW;Kristian A;Zhao Y;Zhou M;Liu Z;Ding Y;Wang B;Mælandsmo GM;Nesland JM;Fodstad O;Tan M
通讯作者：
Tan M
影响因子：
3.7
作者：
Enerly E;Steinfeld I;Kleivi K;Leivonen SK;Aure MR;Russnes HG;Rønneberg JA;Johnsen H;Navon R;Rødland E;Mäkelä R;Naume B;Perälä M;Kallioniemi O;Kristensen VN;Yakhini Z;Børresen-Dale AL
通讯作者：
Børresen-Dale AL