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Androgen receptor suppresses prostate cancer metastasis but promotes bladder cancer metastasis via differentially altering miRNA525-5p/SLPI-mediated vasculogenic mimicry formation.
Cancer Letters ( IF 9.1 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.canlet.2019.12.018
Zhao Yang 1 , Jiaqi Chen 1 , Hongjun Xie 1 , Tianjie Liu 1 , Yule Chen 1 , Zhenkun Ma 1 , Xinqi Pei 1 , Wenjie Yang 1 , Lei Li 1
Affiliation  

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.

中文翻译:

雄激素受体通过差异性改变miRNA525-5p / SLPI介导的血管生成模拟物形成来抑制前列腺癌转移,但促进膀胱癌转移。

早期研究表明,雄激素受体(AR)可能在影响前列腺癌(PCa)和膀胱癌(BCa)转移中起不同作用,但其潜在机制仍不清楚。在这里,我们发现AR可能通过差异性地改变血管生成模拟物(VM)的形成来发挥作用,以降低PCa转移或增加BCa转移。机制剖析表明,AR可以通过miR-525-5p差异调节VM标志物SLPI的表达,从而调节SLPI。此外,它可以通过与位于miR-525前体启动子中不同位置的不同雄激素反应元件(ARE)结合,增加PCa中的miR-525-5p转录或降低其BCa中的转录。进一步,液相色谱-质谱法(LC-MS)的结果表明,PCa和BCa中AR的辅因子分别是NFIX和HDAC2。总之,这些结果提供了第一个详细的机制,说明AR如何差异性地改变PCa和BCa的转移。因此,以新近确定的AR-miR-525-5p-SLPI轴为目标可能有助于抑制转移。
更新日期:2019-12-13
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