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

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.

Keywords: Bone metastasis; NF-κB signaling; Prostate cancer; Serum biomarker; miR-218–5p.