Chromosome 19 miRNA cluster and CEBPB expression specifically mark and potentially drive triple negative breast cancers.
Chromosome 19 miRNA cluster and CEBPB expression specifically mark and potentially drive triple negative breast cancers.
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DOI：
10.1371/journal.pone.0206008
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Brohl AS
中科院分区：
文献类型：
--
作者：
Jinesh GG;Flores ER;Brohl AS
已知三阴性乳腺癌（tnbc）表达低PGR、ESR1和ERBB2，高KRT5、KRT14和KRT17。然而，tnbc中KRT5、KRT14、KRT17表达升高，PGR、ESR1、ERBB2表达降低的原因尚不完全清楚。本研究表明，19号染色体miRNA簇（C19MC）的表达特异性地标记了人类tnbc。低REST和高CEBPB与C19MC、KRT5、KRT14和KRT17的表达相关，这些基因/簇的增强子受CEBPB和REST结合位点的调控。C19MC mirna反过来可以潜在地靶向REST以提供正反馈回路，并可能靶向PGR， ESR1, ERBB2, GATA3, SCUBE2, TFF3 mrna，从而促进TNBC表型。因此，我们的研究表明，C19MC miRNA表达标志着TNBC， C19MC miRNA和CEBPB可能共同决定TNBC标志物的表达模式。
Triple negative breast cancers (TNBCs) are known to express low PGR, ESR1, and ERBB2, and high KRT5, KRT14, and KRT17. However, the reasons behind the increased expressions of KRT5, KRT14, KRT17 and decreased expressions of PGR, ESR1, and ERBB2 in TNBCs are not fully understood. Here we show that, expression of chromosome 19 miRNA cluster (C19MC) specifically marks human TNBCs. Low REST and high CEBPB correlate with expression of C19MC, KRT5, KRT14, and KRT17 and enhancers of these genes/cluster are regulated by CEBPB and REST binding sites. The C19MC miRNAs in turn can potentially target REST to offer a positive feedback loop, and might target PGR, ESR1, ERBB2, GATA3, SCUBE2, TFF3 mRNAs to contribute towards TNBC phenotype. Thus our study demonstrates that C19MC miRNA expression marks TNBCs and that C19MC miRNAs and CEBPB might together determine the TNBC marker expression pattern.
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DOI：
10.1158/1078-0432.ccr-16-2174
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Afghahi A;Timms KM;Vinayak S;Jensen KC;Kurian AW;Carlson RW;Chang PJ;Schackmann E;Hartman AR;Ford JM;Telli ML
通讯作者：
Telli ML
影响因子：
64.8
作者：
Hark, AT;Schoenherr, CJ;Tilghman, SM
通讯作者：
Tilghman, SM
影响因子：
12.4
作者：
Jinesh, G. G.;Choi, W.;Kamat, A. M.
通讯作者：
Kamat, A. M.
影响因子：
7
作者：
Jakobsen JS;Waage J;Rapin N;Bisgaard HC;Larsen FS;Porse BT
通讯作者：
Porse BT
影响因子：
7
作者：
Franco HL;Nagari A;Malladi VS;Li W;Xi Y;Richardson D;Allton KL;Tanaka K;Li J;Murakami S;Keyomarsi K;Bedford MT;Shi X;Li W;Barton MC;Dent SYR;Kraus WL
通讯作者：
Kraus WL