miR-152 通过靶向前列腺癌细胞系中的 TGFα 来控制迁移和侵袭潜能。

miR-152 controls migration and invasive potential by targeting TGFα in prostate cancer cell lines.

机构信息

State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Prostate. 2013 Jul;73(10):1082-9. doi: 10.1002/pros.22656. Epub 2013 Mar 4.

DOI:10.1002/pros.22656

PMID:23460133

Abstract

BACKGROUND

MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152.

METHODS

The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR.

RESULTS

TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152.

CONCLUSIONS

Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.

摘要

背景

MicroRNAs (miRNAs) 是一类短的非编码 RNA，在多种生物学过程中发挥作用。异常表达的 miR-152 在各种恶性肿瘤中经常被报道。然而，miR-152 在前列腺癌 (PCa) 中的作用机制尚不清楚。本研究旨在确定 miR-152 在 PCa 细胞中的功能，并鉴定由 miR-152 调控的新型分子靶标。

方法

通过 Western blot 分析测定三例 PCa 及相邻非肿瘤组织中转化生长因子-α (TGFα) 的表达水平。通过 qRT-PCR 测定 48 例原发性 PCa 和 15 例非恶性组织样本中的 miR-152 水平。通过细胞迁移和侵袭实验以及 Western blot 分析评估强制表达 miR-152 或敲低 TGFα 对 PCa 细胞的影响。双荧光素酶报告基因实验用于鉴定 miR-152 和 TGFα 3'-UTR 之间的结合位点。

结果

与相邻正常组织相比，PCa 组织样本中 TGFα 上调。与非恶性样本相比，原发性 PCa 样本中 miR-152 表达显著降低。Gleason 评分>7 的患者 miR-152 水平低于评分较低的患者。此外，低 miR-152 表达与进展期病理 T 分期相关。强制表达 miR-152 或敲低 TGFα 可显著降低 PCa 细胞的体外迁移和侵袭能力。TGFα 是 miR-152 的直接靶基因。