hZIP1 that is down-regulated in clear cell renal cell carcinoma is negatively associated with the malignant potential of the tumor

Urol Oncol. 2014 Aug;32(6):885-92. doi: 10.1016/j.urolonc.2014.02.021. Epub 2014 May 28.

Abstract

Objective: The human ZRT, IRT-like protein 1 (hZIP1) has been associated with tumorigenesis. However, its role in clear cell renal cell carcinoma (ccRCC) has not been yet reported. The objective was to investigate hZIP1 expression in ccRCC and its association with clinicopathological features.

Materials and methods: A total of 106 ccRCC tissue samples and corresponding normal kidney tissue samples were examined, along with 3 ccRCC cell lines (ACHN, 769-P, and 786-O). Real-time polymerase chain reaction, Western blot, and immunohistochemistry were used to investigate the expression of hZIP1 and its relationship with clinicopathological features. The ACHN cell line, exhibiting the highest hZIP1 expression, was transfected with hZIP1 small interfering RNA or mock small interfering RNA. Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion was determined by Transwell assay.

Results: The level of hZIP1 was decreased in ccRCC tissues when compared with normal tissues. hZIP1 expression significantly decreased with increasing clinical stage and pathological grade in ccRCC samples (P<0.05), showing a significant negative correlation with the histological grade (P<0.05). High hZIP1 expression was associated with a better disease-free survival (P<0.01). Silencing of hZIP1 expression enhanced the proliferative and invasive abilities of ACHN cells.

Conclusions: Results suggest that hZIP1 may act as a tumor suppressor in ccRCC. hZIP1 is closely correlated with clinicopathological features. High hZIP1 expression may be an indicator of good prognosis in ccRCC.

Keywords: Clear cell renal cell carcinoma; Invasion; Metastasis; Prognosis; Proliferation; hZIP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Survival / genetics
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Cation Transport Proteins
  • SLC39A1 protein, human