The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate cancer and underlying mechanism.
The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate cancer and underlying mechanism.
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AR/miR-190a/YB-1负反馈环对前列腺癌的抑制作用及其机制
DOI：
10.1038/srep13528
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发表时间：
2015-08-28
影响因子：
4.6
通讯作者：
Chen K
中科院分区：
文献类型：
--
作者：
Xu S;Wang T;Song W;Jiang T;Zhang F;Yin Y;Jiang SW;Wu K;Yu Z;Wang C;Chen K
由于缺乏有效的治疗方法，晚期前列腺癌（包括转移性和去势抵抗性癌症）仍然无法治愈。miR-190 a属于小分子非编码RNA家族，在乳腺癌转移中具有重要作用。然而，miR-190 a是否在前列腺癌的发展中起作用仍然是未知的。本研究首次观察到AR/miR-190 a/YB-1在前列腺癌中形成了一个自调节负反馈环：miR-190 a的表达被AR激活而下调; YB-1的功能是作为AR激活剂; miR-190 a通过直接结合YB-1基因的3′UTR抑制AR的表达和反式激活。miR-190 a通过AR依赖性信号传导促进人前列腺癌细胞生长。此外，我们检测了miR-190 a的表达，并观察到人类前列腺癌的显著下降。miR-190 a的表达降低与前列腺癌患者的AR水平呈负相关，并且在其肿瘤中具有较高miR-190 a表达的患者具有改善的无肿瘤生存期。总之，我们的研究结果确定了miR-190 a与晚期前列腺癌中表达减少，YB-1和前列腺癌中AR信号传导之间的生物化学和功能联系。
Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. MiR-190a belongs to the small noncoding RNA family and has an important role in breast cancer metastasis. However, it is still unknown whether miR-190a plays a role in prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an auto-regulatory negative feedback loop in prostate cancer: miR-190a expression was down-regulated by AR activation; YB-1 functions are as an AR activator; miR-190a inhibited AR expression and transactivation through direct binding to 3′UTR ofYB-1gene. MiR-190a contributes the human prostate cancer cell growth through AR-dependent signaling. Moreover, we examined the expression of miR-190a and observed a significant decrease in human prostate cancers. Reduced expression of miR-190a was inversely correlated to AR levels of prostate cancer patients and patients with higher miR-190a expression in their tumor have improved tumor-free survival. Taken together, our findings identified a biochemical and functional link between miR-190a with reduced expression in advanced prostate cancer, YB-1 and AR signaling in prostate cancer.