Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer - PubMed (original) (raw)

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

Xiao-Ming Xu et al. Onco Targets Ther. 2016.

Abstract

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.

Keywords: biochemical recurrence-free survival; prostate cancer; solute carrier family 39 member 14; tumor suppressor.

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Figures

Figure 1

Figure 1

Decreased expression of SLC39A14 protein and mRNA in human PCa tissues. Notes: (A) SLC39A14 protein was mainly localized in the membrane and cytoplasm of prostate cells in adjacent noncancerous prostate tissues. Red arrows show strong positive immunostrainings. Magnification, ×400. (B) SLC39A14 protein was weakly expressed in cancer cells in PCa tissues. Magnification, ×400. (C) Statistical analysis revealed that SLC39A14 protein expression levels in human PCa tissues were significantly lower than those in adjacent noncancerous prostate tissues (P<0.01). (D) SLC39A14 mRNA expression levels in human PCa tissues were also lower than those in adjacent noncancerous prostate tissues based on the Taylor dataset (P<0.01). (E) SLC39A14 mRNA expression levels in human PCa tissues were also lower than those in adjacent noncancerous prostate tissues based on our clinical samples (P<0.01). Abbreviations: PCa, prostate cancer; SLC39A14, solute carrier family 39, member 14.

Figure 2

Figure 2

Kaplan–Meier curves of patients with PCa based on SLC39A14 mRNA expression. Notes: (A) There was a significant difference in BCR-free survival between patients with high and low SLC39A14 mRNA expression (_P_=0.017). (B) There was no significant difference in overall survival between patients with high and low SLC39A14 mRNA expression (_P_=0.148). Abbreviations: BCR, biochemical recurrence; PCa, prostate cancer; SLC39A14, solute carrier family 39, member 14.

Figure 3

Figure 3

Downregulation of SLC39A14 promotes cell proliferation of LNCaP cells in vitro. Notes: (A) Western blot analysis showed that SLC39A14 protein expression was significantly upregulated by the transfection of SLC39A14 plasmid (en-SLC39A14 or en-con), but was significantly downregulated by the transfection of SLC39A14 siRNA (si-SLC39A14 or si-con). (B) CCK-8 assay indicated that the cell viability of LNCaP cells with overexpression of SLC39A14 was significantly lower than those of control vector-transfected cells. (C) CCK-8 assay indicated that the cell viability of LNCaP cells with knockdown of SLC39A14 dramatically promoted the cell viability. Abbreviations: CCK-8, Cell Counting Kit-8; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; SLC39A14, solute carrier family 39, member 14; OD, optical density.

Figure 4

Figure 4

Downregulation of SLC39A14 promotes invasion of LNCaP cells in vitro. Notes: Transwell assays clearly revealed that downregulation of SLC39A14 significantly enhanced the invasion activity of LNCaP cells compared to that of control cells at 24 hours after the transfection, while overexpression of SLC39A14 dramatically reduced the cell invasion. Cell invasion of LNCaP cells transfected with en-con (A), en-SLC39A14 (B), si-con (C) and si-SLC39A14 (D). (E) The number of invasive cells after the transfection of en-con and en-SLC39A14. (F) The number of invasive cells after the transfection of si-con and si-SLC39A14. Abbreviation: SLC39A14, solute carrier family 39, member 14.

Figure 5

Figure 5

Downregulation of SLC39A14 promotes migration of LNCaP cells in vitro. Notes: (A) Cell migration of LNCaP cells transfected with en-con, en-SLC39A14, si-con and si-SLC39A14. (B) Inhibition rate of LNCaP cells after the transfection of en-con and en-SLC39A14. (C) Inhibition rate of LNCaP cells after the transfection of si-con and si-SLC39A14. Wound-healing assays demonstrated that downregulation of SLC39A14 significantly enhanced the migration activity of LNCaP cells compared to that of control cells at 24 hours after the transfection, while overexpression of SLC39A14 dramatically reduced the cell migration. Abbreviation: SLC39A14, solute carrier family 39, member 14.

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