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抑制 microRNA-300 通过促进 的表达抑制前列腺癌细胞的黏附、迁移和侵袭。

Inhibition of microRNA-300 inhibits cell adhesion, migration, and invasion of prostate cancer cells by promoting the expression of .

机构信息

Department of Urology, Tangshan Gongren Hospital , Tangshan, P.R. China.

The College of Nursing and Rehabilitation, North China University of Science and Technology , Tangshan, P.R. China.

出版信息

Cell Cycle. 2020 Nov;19(21):2793-2810. doi: 10.1080/15384101.2020.1823730. Epub 2020 Oct 16.

Abstract

Prostate cancer (PC) is the most common malignancy in men. As per recent findings, microRNA-300 (miR-300) were found to be overexpressed in numerous types of cancers. In this study, we aimed to explore the effects of miR-300 on the adhesion, invasion, and migration of PC cells by targeting Disabled 1 (). Firstly, the regulatory role of miRNAs on was predicted by screening PC-related differentially expressed genes (DEGs). Immunohistochemistry was applied to determine the positive protein expression of , after which the target relationship between miR-300 and was examined. Loss-of-function and gain-of-function experiments were conducted to determine cell proliferation, adhesion, migration, invasion capability, and cell cycle of PC cells. Our data illustrated that had a low expression, while miR-300 was expressed at a relatively high level in PC tissues. Moreover, our clinicopathological analysis revealed that there was a correlation between miR-300 and tumor, node, metastases stage, Gleason score, and lymph node metastasis of PC patients. was also found to be poorly expressed in PC based on the findings from the microarray analysis. The results from dual-luciferase reporter gene assay corroborated that miR-300 interacts with . Importantly, overexpression of miR-300 and/or si- resulted in the enhancement of RAC1, MMP2, MMP9, CyclinD1, and CyclinE expressions, whereas the expression of and Rap was reduced in PC cells, thus suggesting that down-regulated miR-300 suppressed proliferation, adhesion, migration, and invasion of PC cells. Collectively, our results provided evidence that down-regulation of miR-300 inhibits the adhesion, migration, and invasion of PC cells.

摘要

前列腺癌 (PC) 是男性最常见的恶性肿瘤。根据最近的研究结果,发现 microRNA-300 (miR-300) 在多种癌症中过表达。在这项研究中,我们旨在通过靶向 Disabled 1 () 来探索 miR-300 对 PC 细胞黏附、侵袭和迁移的影响。首先,通过筛选与 PC 相关的差异表达基因 (DEGs) 来预测 miRNA 对的调节作用。应用免疫组织化学法确定阳性蛋白的表达,然后检查 miR-300 与的靶关系。进行功能丧失和功能获得实验,以确定 PC 细胞的增殖、黏附、迁移、侵袭能力和细胞周期。我们的数据表明在 PC 组织中表达相对较高,而在 PC 组织中表达水平较低。此外,我们的临床病理分析表明 miR-300 与肿瘤、淋巴结、转移分期、Gleason 评分和 PC 患者的淋巴结转移之间存在相关性。基于微阵列分析的结果,也发现在 PC 中表达水平较低。双荧光素酶报告基因检测结果证实 miR-300 与相互作用。重要的是,过表达 miR-300 和/或 si- 导致 RAC1、MMP2、MMP9、CyclinD1 和 CyclinE 的表达增强,而在 PC 细胞中表达减少,这表明下调 miR-300 抑制了 PC 细胞的增殖、黏附、迁移和侵袭。总之,我们的结果提供了证据表明下调 miR-300 抑制了 PC 细胞的黏附、迁移和侵袭。

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本文引用的文献

1
Epidemiology of Prostate Cancer.前列腺癌流行病学
World J Oncol. 2019 Apr;10(2):63-89. doi: 10.14740/wjon1191. Epub 2019 Apr 20.
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