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Upregulation of HRD1 promotes cell migration and invasion in colon cancer

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Abstract

3-Hydroxy-3-methylglutaryl reductase degradation (HRD1) is an E3 ubiquitin ligase that functions by promoting degradation of misfolded proteins in processes such as embryogenesis and rheumatoid arthritis. However, little is known about the role of HRD1 in cancer. The aim of the present study was to investigate the expression pattern and functions of HRD1 in human colon cancer (CC). We found that HRD1 expression was increased significantly in human CC tissues, and its overexpression was associated with TNM stage, tumor differentiation, tumor invasive depth, and distant metastasis. Knockdown of HRD1 using small hairpin (sh) RNA plasmid significantly inhibited CC cell migration and invasion. Furthermore, the silencing of HRD1 decreased the expression of MMP-2 and MMP-9, which is critical for CC cell migration and invasion. Taken together, these results revealed that HRD1 is overexpressed in CC and promotes migration and invasion of CC cells. Inhibition of HRD1 may be considered as an effective anti-CC strategy.

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Abbreviations

HRD1:

3-Hydroxy-3-methylglutaryl reductase degradation

CC:

Colon cancer

ER:

Endoplasmic reticulum

ERAD:

ER-associated degradation

UPR:

Unfolded protein response

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Author notes

  1. Xueming Tan and Xiaolu He have contributed equally to this work.

Authors and Affiliations

  1. Department of Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou St., Nanjing, 210029, Jiangsu, People’s Republic of China

    Xueming Tan & Zhining Fan

  2. Department of Digestive Endoscopy Center, Zhongda Hospital Southest University, Nanjing, 210009, Jiangsu, People’s Republic of China

    Xueming Tan

  3. Department of Apheresis, Nanjing Red Cross Blood Center, Nanjing, 210003, Jiangsu, People’s Republic of China

    Xiaolu He

Authors
  1. Xueming Tan
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  2. Xiaolu He
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  3. Zhining Fan
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Contributions

XT was a major contributor in writing the manuscript. XT and ZF collected and analyzed the experimental data. XT and XH performed the histological examination of CC tissues and performed the experiments of HCC cells. ZF supervised the work of the research group. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhining Fan.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This study was approved and supervised by the Human Ethics Review Board of Nanjing Medical University (Nanjing, China).

Informed consent

Written informed consent was obtained from all the participating patients.

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Cite this article

Tan, X., He, X. & Fan, Z. Upregulation of HRD1 promotes cell migration and invasion in colon cancer. Mol Cell Biochem 454, 1–9 (2019). https://doi.org/10.1007/s11010-018-3447-0

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  • DOI: https://doi.org/10.1007/s11010-018-3447-0

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