ZNFX1 anti-sense RNA 1 promotes the tumorigenesis of prostate cancer by regulating c-Myc expression via a regulatory network of competing endogenous RNAs
ZNFX1 anti-sense RNA 1 promotes the tumorigenesis of prostate cancer by regulating c-Myc expression via a regulatory network of competing endogenous RNAs
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ZNFX1 反义 RNA 1 通过竞争性内源 RNA 的调节网络调节 c-Myc 表达，促进前列腺癌的肿瘤发生
DOI：
10.1007/s00018-019-03226-x
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发表时间：
2020-03-01
影响因子：
8
通讯作者：
Liu, Xiankui
中科院分区：
文献类型：
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作者：
Cui, Xiaolu;Piao, Chiyuan;Liu, Xiankui
ZNFX 1反义RNA 1（ZFAS 1）已被证明在多种人类癌症的肿瘤发生中。然而，ZFAS 1在前列腺癌（PCa）进展中的作用及其潜在机制仍不完全清楚。在本研究中，我们发现ZFAS 1在PCa中上调，ZFAS 1过表达预测不良的临床结果。ZFAS 1过表达可显著促进PCa细胞的增殖、侵袭和上皮-间质转化。此外，我们不仅发现miR-27 a/15 a/16被ZFAS 1靶向，ZFAS 1与它们的miRNA反应元件结合，而且还揭示了它们在PCa中的肿瘤抑制作用。我们还发现，Hippo途径的转导子YAP 1及其合作子TEAD 1是miR-27 a/15 a/16的常见下游靶点。此外，发现H3 K9去甲基化酶KDM 3A是miR-27 a的另一个靶基因。重要的是，YAP 1、TEAD 1和KDM 3A都以雄激素非依赖性方式作为强c-Myc诱导剂。综上所述，我们提出了一个调控网络，其中ZFAS 1能够通过与其上游miRNA的串扰诱导YAP 1、TEAD 1和KDM 3A的表达来增强c-Myc表达，从而全面促进前列腺癌肿瘤发生。
ZNFX1 anti-sense RNA 1 (ZFAS1) has been indicated in the tumorigenesis of various human cancers. However, the role of ZFAS1 in prostate cancer (PCa) progression and the underlying mechanisms remain incompletely understood. In the present study, we discovered that ZFAS1 is upregulated in PCa and that ZFAS1 overexpression predicted poor clinical outcomes. ZFAS1 overexpression notably promoted the proliferation, invasion, and epithelial–mesenchymal transition of PCa cells. Furthermore, we not only discovered that miR-27a/15a/16 are targeted by ZFAS1, which binds to their miRNA-response elements, but also revealed their tumor suppressor roles in PCa. We also identified that the Hippo pathway transducer YAP1, as well as its cooperator, TEAD1, are common downstream targets of miR-27a/15a/16. In addition, H3K9 demethylase KDM3A was found to be another target gene of miR-27a. Importantly, YAP1, TEAD1, and KDM3A all act as strong c-Myc inducers in an androgen-independent manner. Taken together, we suggest a regulatory network in which ZFAS1 is capable of enhancing c-Myc expression by inducing the expression of YAP1, TEAD1, and KDM3A through crosstalk with their upstream miRNAs, thereby globally promoting prostate cancer tumorigenesis.