Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

Abstract EN

Background.

The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial.

Materials and Methods.

The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets.

The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines.

Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets.

Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene.

Results.

The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups.

In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups.

In total, 153 miRNA-205 targets were screened through the three aforementioned methods.

Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway.

CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes.

A statistically significant negative correlation between miRNA-205 and CDK1 was observed.

The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples.

Conclusion.

miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.