miR-564 通过靶向 MLLT3 抑制前列腺癌的转移和增殖。

miR-564 inhibited metastasis and proliferation of prostate cancer by targeting MLLT3.

机构信息

Laboratory Medicine, Yidu Central Hospital of Weifang City, Weifang, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Nov;21(21):4828-4834.

Abstract

OBJECTIVE

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).

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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。