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

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

Author information

1
Department of Orthopedic Surgery, Zhuhai Second People's Hospital, Zhuhai, China.
2
Department of Orthopedic Surgery, The Fifth Hospital Affiliated of Sun Yat-sen University, Zhuhai, China.
3
Department of Orthopedic Surgery, The Affiliated Hospital of Zunyi Medical College, Zunyi, China.
4
Department of Ophthalmology, Zhuhai Second People's Hospital, Zhuhai, China.
5
Department of Pediatrics, The Fifth Hospital Affiliated of Sun Yat-sen University, Zhuhai, China.
6
Department of Orthopedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
7
Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
8
Department of Clinical Cytogenetics, Suzhou Precision Medicine Scientific Ltd., Suzhou, China.
9
Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
10
Department of Orthopedic Surgery, The Fifth Hospital Affiliated of Sun Yat-sen University, Zhuhai, China, hzwzs5y@163.com.

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

PMID:
30870834
DOI:
10.1159/000495473

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