Laboratory Medicine, Yidu Central Hospital of Weifang City, Weifang, Shandong, China.
Eur Rev Med Pharmacol Sci. 2017 Nov;21(21):4828-4834.
MiR-564 has been discovered to be abnormally expressed in human malignancy. Two recent studies suggested that miR-564 plays a role in tumor inhibition in both lung and breast cancer. However, no evidence reported the mechanism and function of miR-564 in prostate cancer (PCa).
The PCa tissues and their adjacent normal tissues were collected from 50 PCa patients. Expressions of miR-564 in tissues and cells were evaluated with RT-qPCR. The MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide] assay, flow cytometry and Western-blot analysis, were applied to detect the proliferation, cell cycle progression and the protein expression of PCa cell lines (PC-3 and DU-145). Migration and invasion of PCa cells were analyzed by Transwell assays. Furthermore, the correlation between miR-564 and MLLT3 was assessed by luciferase reporter assay. Also, the PCa cells were transfected with miR-564 mimics control and inhibitor.
In our present research, miR-564 was found dysregulated in PCa cells and to act as a suppressor in PCa cell proliferation, progression of cell cycle, cell invasion and migration. MLLT3 (also known as Af9) is a proto-oncogene, which has first reported in leukemia, and the regulation of its expression remains incompletely elucidated. Also, it is first reported in our study, suggesting that MLLT3 is a direct target of miR-564. The results also showed a significant negative correlation with miR-564 in PCa cells. Furthermore, up-regulation of MLLT3 attenuates the effects of miR-564 on the ability of PCa cells.
Our research demonstrated the suppressor function of miR-564 in PCa, revealing restoration of miR-564 as a potential therapeutic strategy for the treatment of PCa.
miR-564 在人类恶性肿瘤中异常表达。最近的两项研究表明，miR-564 在肺癌和乳腺癌中都发挥着肿瘤抑制作用。然而，目前尚无证据表明 miR-564 在前列腺癌（PCa）中的机制和功能。
收集 50 例 PCa 患者的 PCa 组织及其相邻正常组织。采用 RT-qPCR 检测组织和细胞中 miR-564 的表达。采用 MTT[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐]比色法、流式细胞术和 Western blot 分析检测 PCa 细胞系（PC-3 和 DU-145）的增殖、细胞周期进展和蛋白表达。通过 Transwell 分析检测 PCa 细胞的迁移和侵袭。此外，通过荧光素酶报告基因检测评估 miR-564 与 MLLT3 之间的相关性。还将 miR-564 模拟物对照和抑制剂转染到 PCa 细胞中。
在本研究中，发现 miR-564 在 PCa 细胞中失调，并作为 PCa 细胞增殖、细胞周期进展、细胞侵袭和迁移的抑制剂。MLLT3（也称为 Af9）是一种原癌基因，最初在白血病中报道，其表达的调控仍不完全清楚。也是我们首次报道，提示 MLLT3 是 miR-564 的直接靶基因。研究结果还表明，miR-564 在 PCa 细胞中与 MLLT3 呈显著负相关。此外，上调 MLLT3 可减弱 miR-564 对 PCa 细胞能力的影响。
本研究证实了 miR-564 在 PCa 中的抑制作用，揭示了恢复 miR-564 作为治疗 PCa 的潜在治疗策略的可能性。
