ABSTRACT
Telomeric repeat binding factor 1 (TERF1) has been identified as a tumor suppressor gene in numerous types of human cancer. However, the expression of TERF1 and its mechanism in prostate cancer (PCa) remains unclear. The present study aimed to explore the expression and functions of TERF1 in PCa. The UALCAN database was used to analyze the differential expression of TERF1 between normal prostate tissue and primary PCa tissue. Cell apoptosis was analyzed by Annexin V/propidium iodide staining, and wound healing and Transwell assays were used to detect the cell migration and invasion abilities, respectively. The cell viability was analyzed using an MTT assay. Reverse transcriptionquantitative PCR and western blotting were used to analyze the mRNA and protein expression levels, respectively, of epithelialmesenchymal transition (EMT) markers following TERF1 knockdown in the PC3 cell line. A dual luciferase reporter assay was used to verify the association between TERF1 and microRNA (miR)155 predicted by bioinformatics analysis. Rescue experiments were performed to determine the role of the miR155/TERF1 axis in regulating the cellular behaviors of PCa. The results demonstrated that the expression levels of TERF1 in the primary prostate tumors were significantly downregulated compared with in prostate normal tissue. TERF1 silencing was discovered to significantly promote cell viability, migration and invasion, while suppressing cell apoptosis. The impact of TERF1 on PC3 cells was suggested to occur through the EMT pathway. TERF1 was confirmed to be the direct target of miR155. The overexpression of miR155 promoted the viability, migration and invasion, while suppressing the apoptosis of the PC3 cell line, while the knockdown of miR155 in PC3 cells achieved the opposite trends. In addition, TERF1 overexpression reversed the promotive effects of upregulated miR155 expression levels on the migration and apoptosis of PC3 cells. On the contrary, the knockdown of TERF1 reversed the migration and apoptosis abilities of the downregulated miR155 expression levels on the cellular behaviors of PC3 cells. In conclusion, TERF1, as a direct target of miR155, was discovered to be significantly downregulated in PCa, which was suggested to promote the migration and invasion of PCa via the EMT pathway.
Subject(s)
MicroRNAs/genetics , Prostatic Neoplasms/metabolism , Telomere-Binding Proteins/metabolism , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , MicroRNAs/metabolism , Neoplasm Invasiveness/genetics , PC-3 Cells , Prostate/pathology , Prostatic Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Shelterin Complex , Telomere-Binding Proteins/physiologyABSTRACT
OBJECTIVE: To assess the value of preoperative serum albumin level in predicting the survival of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumor (TURBT). METHODS: Two hundred and sixteen newly diagnosed patients with NMIBC who underwent TURBT between January, 2007 and April, 2012 were retrospectively analyzed. The patients were categorized into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups. The patient survival was estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional analyses were used to determine the hazard ratios (HRs) for the overall survival (OS). RESULTS: Of the patients with available data, 82 (39%) and 127 (61%) patients were classified into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups, respectively. Kaplan-Meier analysis showed a significantly worse 5-year OS in low albumin group than in normal albumin group (P=0.017). In the multivariate Cox regression analysis, after adjusting for confounding variables, the preoperative albumin level remained as an independent predictor for 5-year OS (HR: 3.102, 95%CI: 1.200-8.020, P=0.020). CONCLUSION: A low preoperative albumin level predicts a poor 5-year OS in patients with NMIBC who underwent TURBT. Preoperative serum albumin can be a good prognostic factor for predicting survival of the patients with NMIBC treated with TURBT.