MiR-138-5p inhibits the malignant progression of prostate cancer by targeting FOXC1

Abstract

Background: This study aimed to uncover the effect of miR-138-5p on the proliferation and metastasis of PCa cell lines, and further explore the potential regulatory mechanisms via regulating FOXC1. Methods: 60 pairs cancer tissues and corresponding paracancerous ones from PCa patients were collected to assess the expression level of miR-138-5p by qRT-PCR. Subsequently, over-expression of miR-138-5p were established to explore the proliferation and metastasis of miR-138-5p in PCa cell lines was analyzed by CCK-8, Transwell assay and Wounding healing assay, respectively. Bioinformatics analysis and luciferase reporter gene assay were performed to search for the target genes of miR-138-5p, and FOXC1 was selected. Finally, the biological role of miR-138-5p and FOXC1 in the progression of PCa was clarified by a series of rescue experiments. Results: The results of qRT-PCR revealed that miR-138-5p was lowly expressed in PCa tissues and cell lines. Besides, the PCa patients with low-miR-138-5p had a high Gleason score, lymph node metastasis and poor prognosis of PCa, compared with these patients with high-miR-138-5p. Over-expression of miR-138-5p inhibited the proliferative, migratory and invasive capacities of PC-3 and DU-145 cells. Bioinformatics analysis and luciferase reporter gene assay suggested that FOXC1 was predicted to be the target gene of miR-138-5p. Moreover, FOXC1 expression level was negatively correlated to that of miR-138-5p in PCa tissues. Importantly, over-expression of FOXC1 could reverse miR-138-5p mimic induced-inhibition of PCa malignant progression. Conclusions: Downregulated miR-138-5p was closely associated with high Gleason score, more lymph node metastasis and poor prognosis of PCa patients. In addition, miR-138-5p alleviated the malignant progression of PCa by targeting and downregulating FOXC1.