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APRIL depletion induces cell cycle arrest and apoptosis through blocking TGF-β1/ERK signaling pathway in human colorectal cancer cells

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Abstract

It is well documented that a proliferation-inducing ligand (APRIL), a newly found member of tumor necrosis factor superfamily, overexpressed in the majority of malignancies, plays a potential role in the occurrence and development of these tumors. Herein, we demonstrated that APRIL depletion by using RNA interference in human colorectal cancer (CRC) COLO 205 and SW480 cells resulted in cell proliferation inhibition and evoked cell cycle arrest in G0/G1 phase and apoptosis, coupled with decrease in CDK2, Cyclin D1, Bcl-2 expression and an increase of p21 and Bax expression. In addition, the decreased expression of transforming growth factor-β1 (TGF-β1) and p-ERK was also showed in siRNA-APRIL transfected COLO 205 and SW480 cells, whereas the protein expression levels of Smad2/3, p-Smad2/3, and ERK were not significantly changed. Taken together, our results indicate that APRIL depletion induces cell cycle arrest and apoptosis partly through blocking noncanonical TGF-β1/ERK, rather than canonical TGF-β1/Smad2/3, signaling pathway in CRC cells. Moreover, our study highlights APRIL as a potential molecular target for the therapy of CRC.

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Acknowledgments

This study was supported by the National Natural Science Youth Foundation of China (Grant No. 81201351); the Medical Innovation Team Project of Jiangsu Province (Grant No. LJ201133); the Sixth Talent Peaks Project of Jiangsu Province (Grant No. 2012-WSN-066); the Natural Science Foundation of Nantong University (Grant No. 12Z020, 12Z021).

Conflict of interest

The authors declare no conflicts of interest in this work.

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Authors and Affiliations

  1. Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, School of Public Health, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Feng Wang, Hongbin Ni, Guihua Wang, Weifeng Ding, Hui Cong, Shaoqing Ju, Shumei Yang & Huimin Wang

  2. Department of Clinical Laboratory, The Third People’s Hospital of Nantong City, Nantong, 226006, Jiangsu, People’s Republic of China

    Lin Chen

Authors
  1. Feng Wang
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  2. Lin Chen
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  3. Hongbin Ni
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  4. Guihua Wang
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  5. Weifeng Ding
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  6. Hui Cong
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  7. Shaoqing Ju
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  9. Huimin Wang
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Corresponding authors

Correspondence to Shumei Yang or Huimin Wang.

Additional information

Feng Wang and Lin Chen have contributed equally to this study.

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Wang, F., Chen, L., Ni, H. et al. APRIL depletion induces cell cycle arrest and apoptosis through blocking TGF-β1/ERK signaling pathway in human colorectal cancer cells. Mol Cell Biochem 383, 179–189 (2013). https://doi.org/10.1007/s11010-013-1766-8

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  • DOI: https://doi.org/10.1007/s11010-013-1766-8

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