Increased expression of TNFRSF14 indicates good prognosis and inhibits bladder cancer proliferation by promoting apoptosis.

Despite advances in management, bladder cancer remains a principal cause of cancer­associated complications. Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) is dysregulated in certain types of cancer; however, limited data are available on the expression and function of TNFRSF14 in bladder cancer. In the present study, the aim was to evaluate the expression and biological functions of TNFRSF14 in bladder cancer. Firstly, the expression levels of TNFRSF14 in bladder cancer tissue were examined using The Cancer Genome Atlas (TCGA) database. Secondly, reverse transcription­quantitative polymerase chain reaction was utilized to investigate the expression levels of TNFRSF14 in the T24, SW780 and EJ­M3 bladder cancer cell lines. Transfection and Cell Counting kit­8 (CCK­8) assay was used to evaluate whether TNFRSF14 overexpression or silencing would have an effect on cell proliferation of T24 and EJ­M3 cells. In addition, TNFRSF14­induced apoptotic cells were identified using Annexin V­fluorescein isothiocyanate and propidium iodide staining. Western blot analysis was used to detect proteins associated with the phosphatidylinositol 3­kinase pathway. According to the TCGA dataset, the expression levels TNFRSF14 were decreased in bladder cancer tissue compared with in normal control samples. Patients with bladder cancer exhibiting low expression levels of TNFRSF14 had a worse prognosis compared to those with high expression levels of TNFRSF14. Overexpression of TNFRSF14 in T24 cells led to increased apoptosis and inhibited cell proliferation in vitro. Western blotting demonstrated that TNFRSF14 overexpression increased the expression levels of caspase3­p17 in T24 cells, but significantly decreased the expression levels of phosphorylated (p)­protein kinase B (AKT) and P70 S6 kinase (P70). TNFRSF14 silencing in EJ­M3 cells enhanced cell growth, inhibited cell apoptosis, increased the expression levels of p­AKT and P70, and decreased the expression levels of caspase3­p17. In conclusion, TNFRSF14 may serve a tumor suppressive role in bladder cancer by inducing apoptosis and suppressing proliferation, and act as a novel prognostic biomarker for bladder cancer.

Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer.

OBJECTIVE: Solute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells. PATIENTS AND METHODS: Subcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry. Then, the associations of SLC39A14 expression with various clinicopathological features and clinical outcome of patients with PCa were statistically evaluated. Subsequently, the effects of SLC39A14 overexpression and knockdown on PCa cell proliferation and motility were, respectively, examined by Cell Counting Kit-8, transwell, and wound-healing assays. RESULTS: The immunoreactive scores of SLC39A14 protein in human PCa tissues were significantly lower than those in normal prostate tissues. Based on the Taylor dataset, SLC39A14 downregulation occurred more frequently in patients with PCa with a higher Gleason score (P<0.001), advanced clinical stage (P=0.008), presence of metastasis (P=0.009), and prostate-specific antigen failure (P=0.006). More interestingly, the survival analysis identified SLC39A14 as an independent factor for predicting the biochemical recurrence-free survival of patients with PCa (P=0.017). Functionally, the enforced expression of SLC39A14 could suppress cell proliferation, invasion, and migration of PCa cell lines in vitro, which could be reversed by the knockdown of SLC39A14. CONCLUSION: Decreased expression of SLC39A14 may lead to malignant phenotypes of PCa cells and aggressive tumor progression in patients with PCa. Importantly, SLC39A14 may function as a tumor suppressor and a biomarker for screening patients with biochemical recurrence following radical prostatectomy.