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Tumor Biology

, Volume 35, Issue 7, pp 7177–7185 | Cite as

Concomitant upregulation of nucleostemin and downregulation of Sox2 and Klf4 in gastric adenocarcinoma

  • Malek Hossein Asadi
  • Ali Derakhshani
  • Seyed Javad Mowla
Research Article

Abstract

Nucleostemin (NS) is a nucleolar protein involved in stem cell (SC) self-renewal by controlling cell cycle progression. In addition to SCs, NS is also expressed in some highly proliferating cells including several adult stem cells and cancer cell lines. NS knock-down in different cell lines demonstrated its cell type-dependent function in arresting cell cycle in either G1 or G2/M phases. Here, we have evaluated the expression of NS and iPS genes in 36 gastric cancer and their matched marginal nontumor tissues by means of real-time polymerase chain reaction (RT-PCR). We have also examined a potential causative role of NS in gastric tumorigenesis by suppressing its expression in a gastric cancer cell line, AGS. Our data revealed that NS expression level is much higher in tumor tissues (p = 0.046), especially in high-grade ones (p < 0.001), whereas the expression of Klf4 and Sox2 is downregulated in tumor tissues compared to marginal nontumor samples (p < 0.001). Furthermore, NS suppression in the AGS cell line caused some morphological alterations, a cell cycle arrest at G1 phase, and an upregulation of iPS genes: Nanog, Sox2, and Klf4. Based on our results, NS overexpression seems to have a causative role in gastric tumorigenesis and/or progression, and it could be considered as a potential tumor marker for diagnosis, molecular classification, and molecular therapy of gastric adenocarcinoma.

Keywords

Nucleostemin Gastric cancer RNAi Cancer stem cell iPS 

Notes

Acknowledgments

We thank Dr. Hamid-Reza Kalhor for his valuable comments. This work was supported, in part, by a research grant from the Iranian stem cell network.

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Malek Hossein Asadi
    • 1
    • 2
  • Ali Derakhshani
    • 1
  • Seyed Javad Mowla
    • 2
  1. 1.Department of Biotechnology, Institute of Science and High Technology and Environmental SciencesGraduate University of Advanced TechnologyKermanIran
  2. 2.Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran

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