Upregulation of HRD1 promotes cell migration and invasion in colon cancer
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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.
KeywordsHRD1 Migration Invasion Colon cancer
3-Hydroxy-3-methylglutaryl reductase degradation
Unfolded protein response
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
This study was approved and supervised by the Human Ethics Review Board of Nanjing Medical University (Nanjing, China).
Written informed consent was obtained from all the participating patients.
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