Department of Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China.
Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China.
Biomed Pharmacother. 2018 Dec;108:574-583. doi: 10.1016/j.biopha.2018.09.053. Epub 2018 Sep 20.
Accumulating evidence suggests that microRNA-326 (miR-326) serves as a tumor suppressor in the initiation and progression of several human malignancies. However, the biological function and underlying molecular mechanism of miR-326 in prostatic carcinoma (PCa) remains largely unknown. In the present study, we found that miR-326 expression level was significantly downregulated in both primary PCa and castration-resistant PCa (CRPC) tissue samples as detected by qRT-PCR. Downregulation of miR-326 was closely associated with aggressive progression and poor prognosis of primary PCa patients. Gain- and lose- functional experiments revealed that forced expression of miR-326 significantly inhibited cell proliferation, colony formation, migration and invasion, induced G0/G1 cell cycle arrest, and promoted apoptosis in PCa cells in vitro, whereas, knockdown of miR-326 expression showed the opposite results. Overexpression of miR-326 also suppressed tumor growth in xenografted nude mice in vivo. Moreover, Luciferase reporter, qRT-PCR, and western blot assays identified that the 3'-untranslated region (3'-UTR) of Mucin1 (MUC1) was a direct target region of miR-326. Spearman's correlation analysis also confirmed an inverse relationship between miR-326 and MUC1 expressions in primary PCa tissue samples. In addition, restoration of MUC1 expression effectively abrogated the inhibitory effects of miR-326 on PCa proliferation, invasion and migration through the activation of JNK signaling pathway. Therefore, these data indicated that miR-326 functioned as a tumor suppressor in PCa by negatively regulating MUC1, and that miR-326 might serve as a potential therapeutic candidate for PCa treatment.
越来越多的证据表明，微小 RNA-326（miR-326）在多种人类恶性肿瘤的发生和发展中起着肿瘤抑制因子的作用。然而，miR-326 在前列腺癌（PCa）中的生物学功能和潜在分子机制在很大程度上仍是未知的。在本研究中，我们通过 qRT-PCR 发现 miR-326 的表达水平在原发性 PCa 和去势抵抗性 PCa（CRPC）组织样本中均显著下调。miR-326 的下调与原发性 PCa 患者侵袭性进展和不良预后密切相关。过表达和敲低实验显示，miR-326 的强制表达可显著抑制 PCa 细胞的增殖、集落形成、迁移和侵袭，诱导 G0/G1 细胞周期停滞，并促进细胞凋亡，而敲低 miR-326 的表达则显示出相反的结果。miR-326 的过表达也能抑制异种移植裸鼠体内的肿瘤生长。此外，荧光素酶报告、qRT-PCR 和 Western blot 检测证实，Mucin1（MUC1）的 3'-非翻译区（3'-UTR）是 miR-326 的直接靶区。Spearman 相关分析也证实了 miR-326 和 MUC1 在原发性 PCa 组织样本中的表达呈负相关。此外，MUC1 表达的恢复通过激活 JNK 信号通路有效地消除了 miR-326 对 PCa 增殖、侵袭和迁移的抑制作用。因此，这些数据表明，miR-326 通过负调控 MUC1 在 PCa 中发挥肿瘤抑制作用，miR-326 可能成为治疗 PCa 的潜在治疗候选物。
