Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer.
Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer.
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DOI：
10.18632/oncotarget.21688
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发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Yasui W
中科院分区：
文献类型：
--
作者：
Sekino Y;Sakamoto N;Goto K;Honma R;Shigematsu Y;Sentani K;Oue N;Teishima J;Matsubara A;Yasui W
多西紫杉醇是治疗转移性去势抵抗前列腺癌(CRPC)的标准化疗药物。然而，由于多西紫杉醇耐药性的发展，几乎所有的患者最终都变得难治性。转录的超服务区(T-UCRs)是一类新的非编码RNA，在物种间绝对保守，参与包括前列腺癌(PC)在内的肿瘤发生。在这项研究中，我们研究了26个有代表性的T-UCR的转录水平，并确定了在PC中差异表达的区域。实时定量聚合酶链式反应分析显示T-UCRUC.63+在PC组织中的表达增加。四甲基偶氮唑盐比色法和创伤愈合实验表明UC.63+参与了细胞的生长和迁移。MIR-130b被预测在UC.63+序列中具有结合位点。MiR-130b的表达受到UC.63+过表达或下调的显著干扰。我们还发现UC.63+通过miR-130b调控MMP2的表达。此外，UC.63+的过表达增加了AR及其下游分子PSA的表达，并通过AR调节促进了对多西紫杉醇的耐药性。在接受多西紫杉醇治疗的患者中，多西紫杉醇耐药患者血清UC.63+的表达高于多西紫杉醇敏感患者(P=0.011)。Kaplan-Meier分析显示，血清UC.63+高表达与预后不良相关(P=0.020)。这些结果有力地支持了Uc.63+通过与miR-130b相互作用在PC进展中发挥的重要作用，并表明Uc.63+可能成为决定CRPC患者最佳治疗方案的一个有前途的血清标志物。
Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.
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DOI：
10.1056/nejmoa1503747
发表时间：
2015-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sweeney CJ;Chen YH;Carducci M;Liu G;Jarrard DF;Eisenberger M;Wong YN;Hahn N;Kohli M;Cooney MM;Dreicer R;Vogelzang NJ;Picus J;Shevrin D;Hussain M;Garcia JA;DiPaola RS
通讯作者：
DiPaola RS
影响因子：
8
作者：
Lujambio, A.;Portela, A.;Liz, J.;Melo, S. A.;Rossi, S.;Spizzo, R.;Croce, C. M.;Calin, G. A.;Esteller, M.
通讯作者：
Esteller, M.
影响因子：
5.7
作者：
Sakamoto N;Naito Y;Oue N;Sentani K;Uraoka N;Oo HZ;Yanagihara K;Aoyagi K;Sasaki H;Yasui W
通讯作者：
Yasui W
来自FFPE组织的高miR-21表达与结肠癌中辅助化疗的生存不良和对辅助化疗的反应有关。
影响因子：
6.4
作者：
Oue, Naohide;Anami, Katsuhiro;Schetter, Aaron J.;Moehler, Markus;Okayama, Hirokazu;Khan, Mohammed A.;Bowman, Elise D.;Mueller, Annett;Schad, Arno;Shimomura, Manabu;Hinoi, Takao;Aoyagi, Kazuhiko;Sasaki, Hiroki;Okajima, Masazumi;Ohdan, Hideki;Galle, Peter R.;Yasui, Wataru;Harris, Curtis C.
通讯作者：
Harris, Curtis C.
影响因子：
--
作者：
Olivieri, Michele;Ferro, Matteo;Cimmino, Amelia
通讯作者：
Cimmino, Amelia