miR-21-3p is a positive regulator of L1CAM in several human carcinomas
miR-21-3p is a positive regulator of L1CAM in several human carcinomas
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DOI：
10.1016/j.canlet.2014.08.020
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发表时间：
2014-11-28
期刊：
影响因子：
9.7
通讯作者：
Altevogt, Peter
中科院分区：
文献类型：
--
作者：
Doberstein, Kai;Bretz, Niko P.;Altevogt, Peter
L1细胞粘附分子（L1 CAM）的表达经常发生在人类癌症中，并且与诸如卵巢癌、子宫内膜癌、乳腺癌、肾细胞癌和胰腺导管腺癌的癌症的不良预后相关。L1 CAM促进细胞运动、侵袭、化学抗性和转移形成。阐明参与癌症中L1 CAM表达的遗传过程是相当重要的。转录因子如SLUG、β-连环蛋白/TCF-LEF、PAX 8和VHL已涉及各种类型癌症中L1 CAM的再活化。越来越多的证据表明，微小RNA也可以对基因表达产生强烈影响。在这里，我们已经确定了miR-21- 3 p作为L1 CAM表达的正调控因子。过表达miR-21- 3 p（miR-21*）而非互补序列miR-21- 5 p（miR-21）可通过涉及L1 CAM基因转录激活的未知机制强烈增强肾、子宫内膜和卵巢癌衍生细胞系中的L1 CAM表达。在肾癌、子宫内膜癌和卵巢癌患者队列中，我们观察到L1 CAM和miR-21- 3 p表达的强正相关性。尽管L1 CAM单独是总体和无病生存期的可靠标志物，但L1 CAM和miR-21- 3 p表达的组合强烈增强了预测能力。我们的研究结果为癌症中L1 CAM的复杂调控提供了新的线索，并倡导将L1 CAM/miR-21- 3 p用于诊断应用。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Expression of L1 cell adhesion molecule (L1 CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1 CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1 CAM in cancers is of considerable importance. Transcription factors such as SLUG, beta-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1 CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1 CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1 CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1 CAM and miR-21-3p expressions. Although L1 CAM alone was a reliable marker for overall and disease free survival, the combination of L1 CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1 CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. (C) 2014 Elsevier Ireland Ltd. All rights reserved.