Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals
Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals
复制标题
雄激素受体 (AR) 通过改变 circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 信号促进透明细胞肾细胞癌 (ccRCC) 迁移和侵袭
DOI：
10.1016/j.canlet.2016.12.036
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发表时间：
2017-05-28
期刊：
影响因子：
9.7
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Wang, Kefeng;Sun, Yin;Chang, Chawnshang
越来越多的证据表明，雄激素受体（AR）在促进透明细胞肾细胞癌（ccRCC）的转移中发挥着重要作用。详细机制，尤其是 AR 如何通过改变环状 RNA (circRNA) 发挥作用仍不清楚。在这里，我们鉴定了一种新的 circRNA（命名为 circHIAT1），其在 ccRCC 中的表达低于邻近正常组织。靶向 AR 可以通过增加 circHIAT1 表达来抑制 ccRCC 细胞进展。 ChIP 测定和荧光素酶测定表明，AR 通过在转录水平调节其宿主基因海马丰富转录物 1 (HIAT1) 的表达来抑制 circHIAT1 的表达。 AR 抑制 circHIAT1 的结果导致 miR-195-5p/29a-3p/29c-3p 表达失调，从而增加 CDC42 表达，从而增强 ccRCC 细胞迁移和侵袭。通过 circHIAT1 增加这一新发现的信号可抑制 AR 增强的 ccRCC 细胞迁移和侵袭。总之，这些结果表明 circHIAT1 作为转移抑制剂来抑制 AR 增强的 ccRCC 细胞迁移和侵袭。针对这种新发现的 AR-circHIAT1 介导的 miR-195-5p/29a-3p/29c-3p/CDC42 信号可能有助于我们开发潜在的新疗法，以更好地抑制 ccRCC 转移。 (C) 2017 Elsevier B.V. 保留所有权利。
Increasing evidence has demonstrated that the androgen receptor (AR) plays important roles to promote the metastasis of clear cell renal cell carcinoma (ccRCC). The detailed mechanisms, especially how AR functions via altering the circular RNAs (circRNAs) remain unclear. Here we identified a new circRNA (named as circHIAT1) whose expression was lower in ccRCCs than adjacent normal tissues. Targeting AR could suppress ccRCC cell progression via increasing circHIAT1 expression. ChIP assay and luciferase assay demonstrated that AR suppressed circHIAT1 expression via regulating its host gene, Hippocampus Abundant Transcript 1 (HIAT1) expression at the transcriptional level. The consequences of AR suppressed circHIAT1 resulted in deregulating miR-195-5p/29a-3p/29c-3p expressions, which increased CDC42 expression to enhance ccRCC cell migration and invasion. Increasing this newly identified signal via circHIAT1 suppressed AR-enhanced ccRCC cell migration and invasion. Together, these results suggested that circHIAT1 functioned as a metastatic inhibitor to suppress AR-enhanced ccRCC cell migration and invasion. Targeting this newly identified AR-circHIAT1-mediated miR-195-5p/29a-3p/29c-3p/CDC42 signals may help us develop potential new therapies to better suppress ccRCC metastasis. (C) 2017 Elsevier B.V. All rights reserved.