Down-regulation of RE-1 silencing transcription factor (REST) in advanced prostate cancer by hypoxia-induced miR-106b~25.
Down-regulation of RE-1 silencing transcription factor (REST) in advanced prostate cancer by hypoxia-induced miR-106b~25.
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DOI：
10.1016/j.yexcr.2013.09.020
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发表时间：
2014-01-15
影响因子：
3.7
通讯作者：
Andrisani, Ourania M.
中科院分区：
文献类型：
--
作者：
Liang, Hongzi;Studach, Leo;Hullinger, Ronald L.;Xie, Jun;Andrisani, Ourania M.
关键词：
临床侵袭性前列腺癌（PCa）与雄激素抵抗、转移和神经内分泌标志物的表达有关。为了理解PCa上皮细胞的神经内分泌分化（NED）的机制，我们比较了胚胎发生期间在神经嵴（NC）细胞的原代培养物中发生的神经元分化和PCa细胞系（LNCaP和PC 3）中的NED。我们证明，缺氧分别通过诱导miR-106 b ~25簇促进NC细胞和PCa细胞的神经元和神经内分泌分化。反过来，由miR-106 b、miR-93和miR-25组成的miR-106 b ~25下调转录抑制因子REST，REST抑制神经元特异性蛋白编码基因和miRNA基因。在高Gleason评分（≥ 8）的前列腺肿瘤中，观察到REST和miR-106 b ~25诱导之间的相反趋势。采用miRNA PCR阵列，我们鉴定了LNCaP细胞中缺氧上调的miRNA和NC细胞中REST敲低的miRNA。值得注意的是，在高Gleason评分（≥ 8）的PCa中，一组miRNA（miR-9、miR-25、miR-30 d和miR 302 b）表达上调，提示NED可能是导致PCa恶性的一种机制。我们认为，REST的缺失和这组microRNA的诱导可以作为晚期PCa的潜在新的临床标志物。
Clinically aggressive prostate cancer (PCa) is linked to androgen resistance, metastasis, and expression of neuroendocrine markers. To understand mechanism(s) of neuroendocrine differentiation (NED) of PCa epithelia, we compared neuronal differentiation occurring during embryogenesis, in primary cultures of neural crest (NC) cells, and NED in PCa cell lines (LNCaP and PC3). We demonstrate, hypoxia promotes neuronal and neuroendocrine differentiation of NC cells and PCa cells, respectively, by inducing the miR-106b~25 cluster. In turn, miR-106b~25 comprised of miR-106b, miR-93 and miR-25, down-regulates the transcriptional repressor REST, which represses neuron-specific protein-coding and miRNA genes. In prostate tumors of high Gleason score (≥ 8), an inverse trend was observed between REST and miR-106b~25 induction. Employing miRNA PCR arrays, we identified miRNAs up-regulated by hypoxia in LNCaP cells and REST-knockdown in NC cells. Significantly, a subset of miRNAs (miR-9, miR-25, miR-30d and miR302b) is up-regulated in high Gleason score (≥ 8) PCa, suggesting a mechanism by which NED contributes to PCa malignancy. We propose that loss of REST and induction of this set of microRNAs can serve as potential novel clinical markers of advanced PCa.
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影响因子：
5.3
作者：
Liang, Hongzi;Fekete, Donna M.;Andrisani, Ourania M.
通讯作者：
Andrisani, Ourania M.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
3.3
作者：
Drake, Justin M.;Strohbehn, Garth;Henry, Michael D.
通讯作者：
Henry, Michael D.
影响因子：
21.3
作者：
Ma, Li;Young, Jennifer;Prabhala, Harsha;Pan, Elizabeth;Mestdagh, Pieter;Muth, Daniel;Teruya-Feldstein, Julie;Reinhardt, Ferenc;Onder, Tamer T.;Valastyan, Scott;Westermann, Frank;Speleman, Frank;Vandesompele, Jo;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.