ABSTRACT
Abnormal expression of circular RNA (circRNA) is tightly linked to cancer progression. In this study, we aimed to investigate the biological role of circ_0076305 in prostate cancer (PCa). RT-qPCR was utilized to examine circ_0076305, microRNA-411-5p (miR-411-5p) and phosphoglycerate kinase 1 (PGK1) expression in PCa tissues and cells. CCK-8 assay, EdU assay, wound-healing assay and flow cytometry were executed to investigate the regulatory function of circ_0076305 on the proliferation, migration and apoptosis of PCa cells. Western blot (WB) assay was applied for measuring the protein levels. The effect of circ_0076305 on cellular glycolysis was examined using commercial kits. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were conducted for confirming the association between miR-411-5p and circ_0076305 or PGK1. The role of circ_0076305 in vivo was detected via establishing mice xenograft model. Circ_0076305 was highly expressed in PCa. Circ_0076305 silencing could repress cell growth, migration and glycolysis while triggered apoptosis in PCa cells. MiR-411-5p was targeted by circ_0076305, and miR-411-5p suppression counteracted the influence of circ_0076305 silencing in PCa cells. Additionally, miR-411-5p directly targeted PGK1, and miR-411-5p upregulation restrained PCa cell malignant behaviours via reducing PGK1. Mechanically, circ_0076305 sponged miR-411-5p to affect PGK1 expression. Importantly, circ_0076305 interference inhibited tumour growth in vivo. Circ_0076305 served as a novel oncogene PCa progression through regulation of miR-411-5p/PGK1 axis.
Subject(s)
MicroRNAs , Prostatic Neoplasms , Animals , Cell Movement/genetics , Cell Proliferation/genetics , Humans , Male , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Phosphoglycerate Kinase/genetics , Prostatic Neoplasms/genetics , RNA, Circular/geneticsABSTRACT
MicroRNAs (miRNAs) are well established key players in tumorigenesis. Their emergence as potential diagnostic and prognostic biomarkers for cancer has demonstrated the importance of miRNAs in cancer biology. Although miR486 is implicated in many types of cancer, its role in renal cell carcinoma (RCC) remains undetermined. In the present study, realtime quantitative PCR (qPCR), wound scratch assay, cell proliferation assay, Transwell migration assay and flow cytometry were utilized to detect the miR486 transcript and its role in proliferation, migration and apoptosis in RCC. The relationship between miR486 expression and clinicopathological variables or overall survival was analyzed using 96 formalinfixed paraffinembedded (FFPE) RCC samples. The results of the present study revealed significant upregulation of miR486 in RCC tissues and cell lines. Moreover, ectopic expression of miR486 promoted cell proliferation, mobility and inhibited apoptosis in 786O and ACHN cell lines. In addition, the Cox proportional hazard regression analysis revealed that patients with low expression of miR486 exhibited a markedly longer overall survival in the univariate and multivariate analyses. In conclusion, our findings indicate that miR486 may serve as a novel prognostic biomarker but may also be applied as a new therapeutic approach for the treatment of RCC.