Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression
Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression
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雄激素诱导的 miR-27A 通过靶向 MAP2K4 充当肿瘤抑制因子并介导前列腺癌进展
DOI：
10.1016/j.biocel.2016.08.043
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发表时间：
2016-10-01
影响因子：
4
通讯作者：
Li, Yao
中科院分区：
文献类型：
--
作者：
Wan, Xuechao;Huang, Wenhua;Li, Yao
前列腺癌（PCa）是男性中最常见的诊断和第二大癌症死亡原因。但前列腺癌进展的确切机制，包括microRNAs（miRNAs）在其中的作用，仍需进一步研究。我们发现miR-27 a在前列腺癌中下调，我们研究了miRNA-27 a在前列腺癌中的机制和作用。AR的转录靶点MiR-27 a是LNCaP细胞中雄激素诱导的miRNA。在去势抵抗性前列腺癌（CRPC）细胞中，我们首次报道了miR-27 a通过PI 3 K信号转导下调。miR-27 a在前列腺癌中起肿瘤抑制剂的作用。过表达miR-27 a可降低前列腺癌细胞的增殖和迁移能力，诱导前列腺癌细胞周期阻滞和凋亡。MAP 2K 4是miR-27 a的直接靶基因，在前列腺癌中作为癌基因发挥作用，其作用是减少前列腺癌细胞的G1-S期阻滞和抑制细胞凋亡。综上所述，miR-27 a通过抑制前列腺癌细胞系中的癌基因MAP 2K 4发挥抑癌作用;我们还提供了miR-27 a介导的去势抵抗性前列腺癌的新机制，即雄激素剥夺治疗（ADT）后异常AR信号和PI 3 K/Akt信号引起的miR-27 a下调将促进去势抵抗性前列腺癌的进展。(C)2016爱思唯尔有限公司版权所有。
Prostate cancer (PCa) is the most commonly diagnosed and secondly leading cause of cancer death among males. But the precise mechanism of prostate cancer progression, including microRNAs (miRNAs) functioning in it, is still needs further study. We found miR-27a to be down-regulated in prostate cancer, and we investigated the mechanism and role of miRNA-27a in prostate cancer. MiR-27a, a transcriptional target of AR, was an androgen-induced miRNA in LNCaP cells. In castration-resistant prostate cancer (CRPC) cells, we for the first time reported that miR-27a was downregulated by PI3K signaling. MiR-27a functioned as a tumor suppressor in prostate cancer. Over-expression of miR-27a decreased prostate cancer cell proliferation and migration, and induced prostate cancer cell cycle arrest and apoptosis. MAP2K4, miR-27a's direct target gene, functioned as an oncogene in prostate cancer by reducing G1-S phase arrest and inhibiting cell apoptosis of prostate cancer cells. In conclusion, miR-27a functions as a tumor suppressor by suppressing MAP2K4 which acts as an oncogene in prostate cancer cell lines; we also provided a new mechanism of castration-resistant prostate cancer mediated by miR-27a that downregulation of miR-27a caused by aberrant AR signaling and PI3K/Akt signaling after androgen deprivation therapy (ADT) would promote the progression of castration-resistant prostate cancer. (C) 2016 Elsevier Ltd. All rights reserved.