Decreased expression of SLC39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer

Abstract

ObjectiveSolute 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 methodsSubcellular 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.ResultsThe 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.ConclusionDecreased 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.

A guide to plasma membrane solute carrier proteins

“…In fact, a comparison of healthy and cancerous cell lines suggested that SLC proteins have greater changes in their coexpression networks than protein kinases [28]. Proteins like SLC2A1, SLC39A14, and SLC16A1 may serve as prognostic biomarkers in cancers due to their central role in the development of cancer and responses to treatments [551][552][553]. Thus, it is imperative to continue studying transport proteins in a comprehensive manner, focusing not only on individual transport functions, but also unraveling the complex relationships between different transporters and metabolic states.…”

Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo

“…ZIP14 is localized to the plasma membrane and endosome, and expressed in the small intestine, liver, pancreas, and heart [ 85 , 86 ]. Recent studies have shown that ZIP14 is highly expressed in the various cancers in human including the colorectal cancer, hepatocellular cancer, and prostate cancer [ 87 , 88 , 89 , 90 ]. In Zip14 -KO mice with dwarf body sizes, osteopenia, and impaired skeletal growth, cellular and molecular investigations revealed that ZIP14 modulates G protein-coupled receptor-mediated cAMP-CREB signaling by suppressing basal phosphodiesterase (PDE) activity ( Figure 4 D) [ 38 ].…”

A five-DNA methylation signature act as a novel prognostic biomarker in patients with ovarian serous cystadenocarcinoma

“…Researchers have revealed that the aforementioned five methylation sites may be crucial in cancer development. SLC39A14 has been identified as an independent factor for predicting the biochemical recurrence-free survival of patients with prostate cancer, and the decreased expression of SLC39A14 is associated with the tumor aggressiveness of human prostate cancer [ 32 ]. PREX2 (also known as P-Rex2 ) was highly expressed in the brain, heart, skeletal muscle, placenta, and lymph node and promoted cancer cell migration and/or invasion [ 33 – 35 ].…”