Abstract
BackgroundThis 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.Methods60 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.ResultsThe 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.ConclusionsDownregulated 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.
Highlights
This study aimed to uncover the effect of miR-138-5p on the proliferation and metastasis of Prostate cancer (PCa) cell lines, and further explore the potential regulatory mechanisms via regulating Forkhead box C1 (FOXC1)
Results miR‐138‐5p was down‐regulated in PCa tissues and cell lines Data from PCa patients of TCGA were complied for investigating the potential relevant miRNAs associated with the progression of PCa
We firstly focused insight into the expression level of miRNAs form TCGA database, and miR-138-5p was selected and was significant statistical difference in PCa tissues (Fig. 1a). qRT-PCR was performed to evaluate the expression of miR-138-5p in PCa tissues and cell lines
Summary
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. The incidence and mortality rate of PCa in China has rapidly increased year by year, which has become a serious threat to human healthy [4, 5]. When prostate specific antigen (PSA) test was primarily used to screen for PCa before symptoms appear, the detection rate of PCa peaked in the early 1990s [6, 7]. Approximately 85% new diagnosed PCa cases were limited to early-stage cancer [8]. PSA test greatly improved the early-stage diagnostic rate of PCa, its benefit in decreasing the mortality of PCa remained controversial [9, 10]. The malignant progress of PCa is a multi-step and multi-stage process, including inactivation of anti-oncogenes and/or
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