microRNA-877-5p exerts tumor-suppressive functions in prostate cancer through repressing transcription of forkhead box M1.

The study aimed to investigate the significant potential role of miR-877-5p in Prostate cancer. The expression levels of miR-877-5p and forkhead box M1 (FOXM1) mRNA were detected by qRT-PCR. The prognostic significance of miR-877-5p in prostate cancer was investigated using Kaplan Meier analysis. Then, Cell Counting Kit-8 (CCK-8) and transwell assay were used to evaluate the effects of miR-877-5p on cell biological functions. The mechanism of miR-877-5p action on prostate cancer cells was investigated by luciferase activity assay with wide-type or mutation. miR-877-5p was lowly expressed both in prostate cancer tissues and cell lines compared with corresponding normal counterparts. Further, miR-877-5p was significantly correlated with Gleason score and TNM stage. Moreover, miR-877-5p may serve as an independent prognostic predictor. In addition, FOXM1 was checked as a direct target gene of miR-877-5p, and miR-877-5p can inhibit the expression of FOXM1 to restrain the growth, migration, and invasion abilities of prostate cancer cells. Taken together, miR-877-5p may act as a suppressor in prostate cancer and reduces cancer cell proliferation, migration and invasion by targeting FOXM1. miR-877-5p may serve as the effective biomarkers and therapeutic target for treating prostate cancer patients.

Targeting eIF5A2 inhibits prostate carcinogenesis, migration, invasion and metastasis in vitro and in vivo.

Overexpression of eukaryotic initiation factor- 5A2 (eIF5A2) has been implicated in promoting tumor cell migration and invasion in many cancers. However, whether eIF5A2 could be as the target for prostate cancer (PCa) treatment is still unknown. In this study, small interfering RNA specific for eIF5A2 (eIF5A2 siRNA) and lentivector for eIF5A2 shRNA (Lv-eIF5A2 shRNA) was performed to down-regulate eIF5A2 expression in PCa PC-3 M IE8 cells and in animal tumor model, respectively. The biological function of eIF5A2 siRNA or Lv-eIF5A2 shRNA on PC-3 M IE8 cell growth, apoptosis, migration, invasion and lung metastasis were explored. The results showed that targeting eIF5A2 inhibited PC-3 M IE8 cell invasion, migration, proliferation and increased cell apoptosis in vitro, and inhibited tumor growth and lung metastasis in vivo. Analysis of eIF5A2 signaling pathways in the clonal derivatives showed a decrease in MMP-2 and MMP-9 activation and increase in bcl-2 expression. We therefore concluded that therapies targeting the eIF5A2 signaling pathway may be more effective to prevent organ metastasis and primary tumor formation.