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Tumor Biology

, Volume 36, Issue 1, pp 291–302 | Cite as

The over-expression of aquaporin-1 alters erythroid gene expression in human erythroleukemia K562 cells

  • Min Wei
  • Rong Shi
  • Jun Zeng
  • Nisha Wang
  • Jueyu Zhou
  • Wenli Ma
Research Article

Abstract

Aquaporin genes are differentially expressed in primitive versus definitive erythropoiesis. Our previous research results showed that over-expression of aquaporin-1 (AQP1) gene greatly promotes the erythroid differentiation of erythroleukemia K562 cells, using benzidine staining and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis for representative erythroid-related genes, including γ-globin. But the molecular mechanisms underlying erythroid-specific gene regulation remain unknown. In this study, we demonstrated that AQP1 induced hemoglobins expression and altered erythroid gene expression by microarray analysis in K562 cells. The retroviral expression vector of AQP1 (pBABE-puro-AQP1) was constructed and infected K562 cells to establish a stable AQP1 over-expression cell line (K562-AQP1). AQP1 over-expression effectively inhibited cell proliferation and induced cell growth arrest in G1 phase of K562 cells. Then microarray profile was applied to analyze the differentially expressed genes which involved the mechanism of AQP1 in erythroid differentiation induction. The DAVID functional annotation clustering tool was used to identify biological functions enriched with the differentially expressed genes (n = 466 genes) and to group genes into clusters based on their functional similarity. Significant enrichment of genes involved in “oxygen transporter activity” (p = 3.8E-7) including hemoglobins (HBD, HBG, HBB, HBE1, and HBQ1), HEMGN, and EBP42 were validated by qRT-PCR. Moreover, silencing of HEMGN by RNA interference in K562-AQP1 cells resulted in down-regulation of these genes. These data provide a better understanding of the role of AQP1 in erythroid differentiation, by promoting HEMGN induction and other potential signaling pathways associated with hemoglobin induction.

Keywords

AQP1 HEMGN Hemoglobin expression Erythroid differentiation Microarray K562 cells 

Notes

Acknowledgments

This work is supported by the National Natural Science Foundation of China (Grant No. 30901721) and the Natural Science Foundation of Guangdong Province (No. S2012010009537).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Min Wei
    • 1
  • Rong Shi
    • 1
  • Jun Zeng
    • 1
  • Nisha Wang
    • 1
  • Jueyu Zhou
    • 1
  • Wenli Ma
    • 1
  1. 1.Institute of Genetic EngineeringSouthern Medical UniversityGuangzhouPeople’s Republic of China

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