Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer

Liang,Yu-Xiang; Mo,Ru-Jun; He,Hui-Chan; Chen,Jia-Hong; Zou,Jun; Han,Zhao-Dong; Lu,Jian-Ming; Cai,Chao; Zeng,Yan-Ru; Zhong,Wei-De; Wu,Chin-Lee

doi:10.3892/or.2015.3870

Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer

Authors:
- Yu-Xiang Liang
- Ru-Jun Mo
- Hui-Chan He
- Jia-Hong Chen
- Jun Zou
- Zhao-Dong Han
- Jian-Ming Lu
- Chao Cai
- Yan-Ru Zeng
- Wei-De Zhong
- Chin-Lee Wu
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Affiliations: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Department of Urology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Published online on: March 20, 2015 https://doi.org/10.3892/or.2015.3870
Pages: 2648-2654

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Abstract

Our previous study revealed the potential role of CD147 in human prostate cancer (PCa). Here, we investigated the CD147 promoter methylation status and the correlation with tumorigenicity in human PCa. CD147 mRNA and protein expression levels were both significantly higher in the 4 PCa cell lines, than in the 2 non-tumorigenic benign human prostatic epithelial cell lines (all P<0.01). We showed hypomethylation of promoter regions of CD147 in PCa cell lines with significant CD147 expression as compared to non-tumorigenic benign human prostatic epithelial cell lines slowly expressing CD147. Additionally, the treatment of methylated cell lines with 5-aza-2'-deoxycytidine increased CD147 expression significantly in low-expressing cell lines and also activated the expression of matrix metalloproteinase (MMP)-2, which may be one of the most important downstream targets of CD147. Furthermore, PCa tissues displayed decreased DNA methylation in the promoter region of CD147 compared to the corresponding non‑cancerous prostate tissues, and methylation intensity correlated inversely with the CD147 mRNA levels. There was a significant negative correlation between CD147 mRNA levels and the number of methylated sites in PCa tissues (r=-0.467, P<0.01). In conclusion, our data offer convincing evidence for the first time that the DNA promoter hypomethylation of CD147 may be one of the regulatory mechanisms involved in the cancer-related overexpression of CD147 and may play a crucial role in the tumorigenesis of PCa.

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