Androgen receptor suppresses prostate cancer metastasis but promotes bladder cancer metastasis via differentially altering miRNA525-5p/SLPI-mediated vasculogenic mimicry formation
Androgen receptor suppresses prostate cancer metastasis but promotes bladder cancer metastasis via differentially altering miRNA525-5p/SLPI-mediated vasculogenic mimicry formation
复制标题
雄激素受体通过差异改变 miRNA525-5p/SLPI 介导的血管生成拟态形成抑制前列腺癌转移但促进膀胱癌转移
DOI：
10.1016/j.canlet.2019.12.018
复制
发表时间：
2020
期刊：
影响因子：
9.7
通讯作者：
Li Lei
中科院分区：
文献类型：
--
作者：
Yang Zhao;Chen Jiaqi;Xie Hongjun;Liu Tianjie;Chen Yule;Ma Zhenkun;Pei Xinqi;Yang Wenjie;Li Lei
早期研究表明雄激素受体（AR）在影响前列腺癌（PCa）和膀胱癌（BCa）转移中可能发挥不同的作用，但其潜在机制尚不清楚。在这里，我们发现AR可能通过差异性改变血管生成拟态（VM）的形成来减少PCa转移或增加BCa转移。机制分析表明，AR可通过miR-525- 5 p差异性地改变VM标志物SLPI的表达，从而调控SLPI的表达;此外，AR还可通过与位于miR-525前体启动子不同位置的不同雄激素反应元件（战神）结合，增加miR-525- 5 p在PCa中的转录或降低miR-525- 5 p在BCa中的转录。此外，液相色谱-质谱法（LC-MS）的结果显示，PCa和BCa中AR的辅因子分别为NFIX和HDAC 2。总之，这些结果提供了AR如何差异性改变PCa和BCa转移的第一个详细机制;因此，靶向新鉴定的AR-miR-525- 5 p-SLPI轴可能有助于抑制转移。
Early studies suggest that the androgen receptor (AR) may play differential roles in influencing prostate cancer (PCa) and bladder cancer (BCa) metastasis, but the underlying mechanisms remain unclear. Here, we found that the AR might function via differentially altering vasculogenic mimicry (VM) formation to either decrease PCa metastasis or increase BCa metastasis. Mechanism dissection showed that the AR could differentially alter the expression of the VM marker SLPI through miR-525-5p to regulate SLPI; moreover, it could either increase miR-525-5p transcription in PCa or decrease it in BCa via binding to different androgen-response-elements (AREs) located at different positions in the miR-525 precursor promoter. Further, results from liquid chromatography–mass spectrometry (LC-MS) showed that the co-factors of AR in PCa and BCa are NFIX and HDAC2, respectively. Together, these results provide the first detailed mechanism of how the AR can differentially alter PCa and BCa metastasis; thus, targeting the newly identified AR-miR-525-5p-SLPI axis may help suppress metastasis.