血清 miR-218-5p 水平降低可作为前列腺癌骨转移的血清标志物。

Decreased miR-218-5p Levels as a Serum Biomarker in Bone Metastasis of Prostate Cancer.

机构信息

Department of Orthopedic Surgery, Zhuhai Second People's Hospital, Zhuhai, China.

Department of Orthopedic Surgery, The Fifth Hospital Affiliated of Sun Yat-sen University, Zhuhai, China.

出版信息

Oncol Res Treat. 2019;42(4):165-185. doi: 10.1159/000495473. Epub 2019 Mar 14.

DOI:10.1159/000495473

PMID:30870834

Abstract

BACKGROUND

miR-218-5p is an extensively studied microRNA (miRNA) in prostate cancer (PCa). However, the clinical significance and biological role of miR-218-5p in bone metastasis of PCa remain unclear.

MATERIALS AND METHODS

miR-218-5p expression was evaluated in 38 bone metastatic and 115 non-bone metastatic PCa tissues and serum samples. Clinical correlation of miR-218-5p expression with clinicopathological characteristics was analyzed. The biological roles of miR-218-5p in bone metastasis of PCa were investigated in vitro by invasion and migration assays. Bioinformatics analysis, real-time polymerase chain reaction, western blot, and luciferase reporter assay were applied to discern and examine the relationship between miR-218-5p and its potential targets.

RESULTS

miR-218-5p expression was reduced in bone metastatic PCa tissue and serum samples, which positively correlated with poor clinicopathological characteristics and bone metastasis-free survival in PCa patients. Upregulating miR-218-5p repressed PCa cell invasion and migration. Furthermore, miR-218-5p inhibited NF-κB signaling via simultaneously targeting TRAF1, TRAF2, and TRAF5, which suppressed the invasion and migration abilities of PCa cells. ROC curve analysis of miR-218-5p in the serum of PCa patients exhibited an area under the curve of 0.86 (95% confidence interval 0.80-0.92, p < 0.001).

CONCLUSION

Our findings indicate that miR-218-5p might represent a novel serum biomarker for bone metastasis of PCa.

摘要

背景

miR-218-5p 是前列腺癌（PCa）中广泛研究的 microRNA（miRNA）。然而，miR-218-5p 在 PCa 骨转移中的临床意义和生物学作用仍不清楚。

材料和方法

评估了 38 例骨转移和 115 例非骨转移 PCa 组织和血清样本中的 miR-218-5p 表达。分析 miR-218-5p 表达与临床病理特征的临床相关性。通过侵袭和迁移实验在体外研究 miR-218-5p 在 PCa 骨转移中的生物学作用。应用生物信息学分析、实时聚合酶链反应、western blot 和荧光素酶报告基因检测来辨别和检查 miR-218-5p 与其潜在靶标的关系。

结果

miR-218-5p 在骨转移 PCa 组织和血清样本中的表达降低，与 PCa 患者的不良临床病理特征和无骨转移生存呈正相关。上调 miR-218-5p 抑制了 PCa 细胞的侵袭和迁移。此外，miR-218-5p 通过同时靶向 TRAF1、TRAF2 和 TRAF5 抑制 NF-κB 信号通路，抑制了 PCa 细胞的侵袭和迁移能力。ROC 曲线分析 PCa 患者血清中的 miR-218-5p 显示曲线下面积为 0.86（95%置信区间 0.80-0.92，p < 0.001）。