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Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC)

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Tumor Biology

Abstract

NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients’ poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression.

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Acknowledgments

We would like to thank Dr. Martin Holcik (Department of Pediatrics, University of Ottawa) for his kindly donation of pcDNA3-Flag-NF45 plasmid. This work was supported by the Natural Science Foundation of China (No. 81272708).

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Authors and Affiliations

  1. Department of Medical Oncology, Shanghai Cancer Center, Fudan University, No. 270 Dong An Road, Shanghai, 200032, China

    Sujie Ni, Huijie Wang & Weijian Guo

  2. Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Junya Zhu, Jianguo Zhang, Shu Zhang, Mei Li, Runzhou Ni, Jinxia Liu, Huiyuan Qiu & Wenjuan Chen

Authors
  1. Sujie Ni
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  2. Junya Zhu
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  3. Jianguo Zhang
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  4. Shu Zhang
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  5. Mei Li
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  6. Runzhou Ni
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  9. Wenjuan Chen
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  11. Weijian Guo
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Correspondence to Weijian Guo.

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Sujie Ni and Junya Zhu have contributed equally to this work.

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Ni, S., Zhu, J., Zhang, J. et al. Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC). Tumor Biol. 36, 747–756 (2015). https://doi.org/10.1007/s13277-014-2683-5

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  • DOI: https://doi.org/10.1007/s13277-014-2683-5

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