High expression of neuroguidin increases the sensitivity of acute myeloid leukemia cells to chemotherapeutic drugs
- Kejun Chen†1,
- Shuqing Lü†1Email author,
- Hui Cheng†1,
- Gusheng Tang1,
- Min Liu1,
- Hong Zhou1 and
- Jianmin Wang1Email author
© Chen et al.; licensee BioMed Central. 2015
Received: 17 December 2014
Accepted: 8 January 2015
Published: 19 February 2015
Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein. The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells. Proliferation inhibition and apoptosis in NGDN over-expressing myeloid multidrug-resistant leukemia cells (K562/A02-NGDN) was significantly higher than in control K562/A02 cells following treatment with vincristine, etoposide, and epirubicin, indicating that NGDN over-expression can increase the sensitivity of multidrug-resistant leukemia cells to chemotherapeutic drugs. Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.
KeywordsNeuroguidin Acute myeloid leukemia Multidrug-resistant Chemotherapeutic drug mTOR
We previously reported the expression of some genes with unknown functions in myeloid leukemia cell lines and primary leukemia cells from clinical patients [1-3], one of which was homologous to neuroguidin (NGDN) . Jung and colleagues confirmed that NGDN has a similar structure and function to eukaryotic translation initiation factor 4E (eIF4E) binding proteins , which are known to inhibit the cap-dependent protein translation as negative regulators of eIF4E and are involved in tumor cell proliferation, survival, and apoptosis [5-9]. Low expression and high phosphorylation of eIF4E binding protein 1 (4E-BP1) is associated with poor prognosis and tumor invasion . High expression of 4E-BPs enhances tumor cell sensitivity to chemotherapeutic drugs and is associated with favorable clinical prognosis [11-13]. In this study, the effect of NGDN and its mechanism of action in human myeloid leukemia cells were investigated.
Effects of NGDN over-expression on proliferation and apoptosis in multidrug-resistant leukemia cell line K562/A02
Effect of NGDN knock-down in K562/A02 cells
The main genes up-regulated in NGDN knock-down leukemia cells K562/A02-KD compared with negative control cells K562/A02-NC (n = 3, P < 0.05)
Relative mRNA expression level (K562/A02-KD/K562/A02-NC)
Extracellular signal gene
Signal transduction pathway gene
Transcription factor gene
Cell invasion and metastasis-related gene
Overall, the results of this study in vitro confirmed that NGDN over-expression can increase the sensitivity of human myeloid multidrug-resistant leukemia cells to chemotherapeutic drugs, indicating that the high expression of NGDN may be a favorable prognostic factor for patients with acute myeloid leukemia [see Additional file 1]. The specific mechanism of action of NGDN in leukemia cells requires further study.
This work is supported by grants from the National Natural Science Foundation of China [grant numbers 30873042, 81100361 to S.L.].
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