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Aberrant methylation of the 16q23.1 tumor suppressor gene ADAMTS18 promotes tumorigenesis and progression of clear cell renal cell carcinoma

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Abstract

Background

The 16q23.1 tumor suppressor gene (TSG) of ADAMTS18 has been identified to be aberrant methylated in clear cell renal cell carcinoma (ccRCC), and there still exists an unclear situation between its methylation and the progression of ccRCC.

Objective

To analyze the biological function and mechanism of ADAMTS18 gene in the tumorigenesis and progression of ccRCC.

Methods

We examined ADAMTS18 gene methylation using methylation- specific polymerase chain reaction (MSP) in 92 ccRCC primary tumors from September 2017 to May 2018. Using reverse transcriptase PCR (RT-PCR) and immunohistochemical (IHC) assay, the relative expression level of ADAMTS18 was measured in the representative tumor samples with their adjacent normal tissues. Meanwhile, colony formation, cell viability, wound healing, transwell chamber, flow cytometry, and PI staining were performed to confirm the tumor-suppressive function and mechanism of ADAMTS18 gene.

Results

Aberrant methylation was further detected in 47 of the 92 (51.1%) primary tumors and in 8 of the 92 (8.7%) adjacent normal tissues (p < 0.05). Due to the phenomenon of aberrant methylation, ectopic low-level expression of ADAMTS18 gene could result in the promotion of tumorigenesis and progression in ccRCC.

Conclusion

The aberrantly methylated ADAMTS18 gene may be involved in the tumorigenesis and progression of ccRCC.

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Acknowledgements

There is no acknowledgement involved in this manuscript.

Funding

This study was supported by grants from Beijing Natural Science Foundation (#7204316), Beijing Traditional Chinese Medicine Development Fundation (#QN-2020-03) and Peking University Medicine Fund of Fostering Young Scholars’Scientific & Technological Innovation (#BMU2020PYB018).

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Author notes

  1. Ben Xu and Yi-ji Peng contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Urology, National Urological Cancer Center, Peking University First Hospital and Institute of Urology, Peking University, 8 Xishiku Street, Xicheng District, Beijing, 100034, China

    Ben Xu, Yi-ji Peng, Bing-lei Ma & Si-da Cheng

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  1. Ben Xu
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  2. Yi-ji Peng
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  3. Bing-lei Ma
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  4. Si-da Cheng
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Correspondence to Ben Xu.

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This study had been approved by Peking University First Hospital. Informed consent was obtained from all individual participants included in the study.

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Xu, B., Peng, Yj., Ma, Bl. et al. Aberrant methylation of the 16q23.1 tumor suppressor gene ADAMTS18 promotes tumorigenesis and progression of clear cell renal cell carcinoma. Genes Genom 43, 123–131 (2021). https://doi.org/10.1007/s13258-021-01036-9

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  • DOI: https://doi.org/10.1007/s13258-021-01036-9

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