Department of Urology, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315010, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4803-4810. doi: 10.3892/mmr.2018.8417. Epub 2018 Jan 10.
Prostate cancer (PCa) is the second most common type of cancer and the 6th leading cause of cancer‑associated mortality worldwide. Accumulated evidence suggests that PCa initiation and progression are controlled by microRNAs (miRNAs). Therefore, investigating PCa‑associated miRNAs may provide novel biomarkers for the diagnosis and treatment of patients with PCa. In the present study it was demonstrated that miRNA‑136 (miR‑136) expression was significantly downregulated in PCa tissues and cell lines. The resumption of miR‑136 expression suppressed cell proliferation and invasion in PCa cells. Bioinformatics analysis predicted that mitogen‑activated protein kinase kinase 4 (MAP2K4) was a direct target of miR‑136. This prediction was experimentally confirmed by a luciferase reporter assay, RT‑qPCR and western blot analysis. MAP2K4 was highly expressed in PCa tissues and inversely correlated with the miR‑136 expression level. Additionally, the restoration of MAP2K4 expression significantly blocked the inhibitory effects of miR‑136 on cell proliferation and invasion in PCa cells. Therefore, miR‑136 may suppress the proliferation and invasion of PCa cells by targeting MAP2K4 and may be a novel candidate target for cancer therapy against PCa.
前列腺癌 (PCa) 是全球第二大常见癌症类型，也是第六大癌症相关死亡原因。越来越多的证据表明，PCa 的发生和发展受到 microRNAs (miRNAs) 的控制。因此，研究与 PCa 相关的 miRNAs 可能为 PCa 患者的诊断和治疗提供新的生物标志物。本研究表明，miRNA-136 (miR-136) 在 PCa 组织和细胞系中的表达明显下调。恢复 miR-136 的表达可抑制 PCa 细胞的增殖和侵袭。生物信息学分析预测丝裂原活化蛋白激酶激酶 4 (MAP2K4) 是 miR-136 的直接靶标。荧光素酶报告基因检测、RT-qPCR 和 Western blot 分析实验证实了这一预测。MAP2K4 在 PCa 组织中高表达，与 miR-136 的表达水平呈负相关。此外，MAP2K4 的表达恢复显著阻断了 miR-136 对 PCa 细胞增殖和侵袭的抑制作用。因此，miR-136 可能通过靶向 MAP2K4 抑制 PCa 细胞的增殖和侵袭，可能成为针对 PCa 的癌症治疗的新候选靶点。
