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Effect of aberrantly methylated androgen receptor target gene PCDH7 on the development of androgen-independent prostate cancer cells

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Abstract

Background

Androgen-independent prostate cancer (AIPC) is an extremely malignant tumor developed from the androgen dependent (ADPC). However, the mechanism of transition process from ADPC to AIPC remains unknown.

Objective

Here we aimed to identify the androgen receptor (AR) target gene and its roles in AIPC.

Methods

Target genes of AR were identified by ChIP-seq in AIPC cells. AR target gene PCDH7 was detected by real time PCR and western blot. Methylation of PCDH7 was measured by bisulfite sequencing and bisulfite amplicon sequencing. Cell growth, invasion and apoptosis were measured by CCK-8, transwell and flow cytometry, respectively.

Results

AR was significantly enriched in the upstream of PCDH7 gene. The expression of PCDH7 was significantly decreased, while the methylation of PCDH7 was increased in the AIPC cells compared to the ADPC cells. DNA methyltransferase inhibitor significantly suppressed the methylation and increased the mRNA and protein level of PCDH7. Moreover, overexpression of DNMT1 remarkably reduced the mRNA and protein level of PCDH7. DNA methyltransferase inhibitor decreased the cell growth and invasion while promote the cell apoptosis in the AIPC cells. AR significantly target PCDH7, whose hypermethylation may repress cell growth and invasion, and promote apoptosis in AIPC.

Conclusions

This study might provide a novel potential target for the treatment of AIPC.

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Availability of data and materials

The datasets used and/or analyzedduring the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the medical and health science and technology plan of Zhejiang Province (2016KYA176).

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Authors and Affiliations

  1. The Clinical Laboratory of the Second Hospital of Jiaxing, Jiaxing, 314000, China

    Siqi Xu, Xiaoyan Wu, Hongsheng Li, Chenliang Fan, Songjin Chen, Jianwei Guo & Yao Ning

  2. The Clinical Laboratory of the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China

    Zhihua Tao

  3. The Orthopaedics Department of the Second Hospital of Jiaxing, No. 1518, Huancheng North Road, Nanhu District, Jiaxing, 314000, Zhejiang, China

    Xuqi Hu

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  1. Siqi Xu
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  2. Xiaoyan Wu
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  3. Zhihua Tao
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  4. Hongsheng Li
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  5. Chenliang Fan
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  6. Songjin Chen
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  7. Jianwei Guo
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  8. Yao Ning
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  9. Xuqi Hu
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Contributions

Conceptualization: XQ. Data curation: XW. Formal analysis: SQ. Funding acquisition: XQ. Investigation: SQ, JG, YN. Methodology: ZT, HL. Software: CF, SC. Writing—original draft: SQ. Writing—review & editing: XW, HL, CF. All authors read and approved the manuscript.

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Correspondence to Xuqi Hu.

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Xu, S., Wu, X., Tao, Z. et al. Effect of aberrantly methylated androgen receptor target gene PCDH7 on the development of androgen-independent prostate cancer cells. Genes Genom 42, 299–307 (2020). https://doi.org/10.1007/s13258-019-00903-w

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  • DOI: https://doi.org/10.1007/s13258-019-00903-w

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