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UHRF1 Promotes Cell Growth and Metastasis Through Repression of p16ink4a in Colorectal Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To investigate whether ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) expression is upregulated in colorectal cancer (CRC), whether UHRF1 promotes CRC cell growth and migration and the underlying molecular mechanism.

Methods

UHRF1 protein expression was determined in 144 pairs of primary CRC and their corresponding adjacent nontumor tissues by immunohistochemistry with tissue microarrays. UHRF1 mRNA expression was assessed in 20 pairs of the above tissues and four colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction. Associations of UHRF1 expression with demographic and clinicopathologic features were determined. Additionally, the effects of lentiviral-mediated RNA interference (RNAi) of UHRF1 on cell proliferation and migration, cell cycle and apoptosis, and the expression of p16ink4a and p21waf1/cip1 were investigated in CRC cell lines.

Results

UHRF1 was overexpressed in CRC tissues and cell lines. UHRF1 protein expression levels correlated with the presence of lymph nodes (P = 0.005), distal metastasis (P = 0.030), poor Dukes staging (P = 0.001), and absence of p16ink4a expression (P = 0.002). RNAi of UHRF1 inhibited proliferation and migration, and induced apoptosis and cell cycle arrest at the G0/G1 phase. Furthermore, RNAi of UHRF1 enhanced the expression of p16ink4a, but not p21waf1/cip1, in CRC cells.

Conclusions

UHRF1 expression is upregulated in CRC and is associated with the progression of CRC. Moreover, RNAi of UHRF1 decreases proliferation and migration but enhances apoptosis of CRC cells, with increased p16ink4a expression. UHRF1 promotes CRC growth and metastasis, likely by repressing p16ink4a, and thus it may be used as a biomarker or even a therapeutic target for CRC.

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Acknowledgment

Supported by grants from the PhD grant of Shanghai Jiaotong University School of Medicine (grant BXJ201137), the National High Technology Research and Development Program (863 Program) (grant 2009AA02Z118), and the National Basic Research Program of China (973 Program) (grant 2008CB517403). We thank Medjaden Bioscience Limited staff members for their help preparing the manuscript.

Conflict of Interest

None to declare.

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Authors and Affiliations

  1. Department of Surgery, Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China

    Feng Wang PhD, Yong-Zhi Yang MS, Chen-Zhang Shi PhD, Peng Zhang PhD, Yang Zou MD & Huan-Long Qin MD

  2. INCELL Corporation, San Antonio, TX, USA

    Mary Pat Moyer PhD

  3. Department of Pathology, Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China

    Hui-Zhen Zhang MD

Authors
  1. Feng Wang PhD
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  2. Yong-Zhi Yang MS
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  3. Chen-Zhang Shi PhD
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  4. Peng Zhang PhD
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  5. Mary Pat Moyer PhD
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  6. Hui-Zhen Zhang MD
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  7. Yang Zou MD
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  8. Huan-Long Qin MD
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Correspondence to Huan-Long Qin MD.

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Wang, F., Yang, YZ., Shi, CZ. et al. UHRF1 Promotes Cell Growth and Metastasis Through Repression of p16ink4a in Colorectal Cancer. Ann Surg Oncol 19, 2753–2762 (2012). https://doi.org/10.1245/s10434-011-2194-1

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  • DOI: https://doi.org/10.1245/s10434-011-2194-1

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