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Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma

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Abstract

The aberrant expression of SPANXA1/A2 (sperm protein associated with the nucleus on the X-chromosome, family members A1/A2) has been observed in multi types of cancers. However, the roles of SPANXA1/A2 in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. The expression of SPANXA1/A2 was evaluated via analyzing UCSC XENA and GEO databases. To dissect the underlying cause of silencing SPANXA1/A2-mediated suppression, cell migration and invasion were detected in SPANXA1/A2 manipulated cell lines. Western blot was performed to evaluate EMT-related factors. The methylation microarray data of SPANXA1/A2 in HNSCC from the UCSC XENA database were used to identify whether aberrant overexpressed SPANXA1/A2 is induced by aberrant DNA methylation. SPANXA1/A2 was highly expressed in tumor tissues and associated with poor survival of patients with HNSCC. Knockdown of SPANXA1/A2 inhibited migration and invasion abilities in both Cal-27 and SCC-9 cells through epithelial–mesenchymal transition (EMT) suppression. The SPANXA1/A2 expression negatively related to its DNA methylation level. SPANXA1/A2 DNA hypomethylation was associated with metastatic stage and poor survival of patients with HNSCC. A dose-dependent increase of SPANXA1/A2 mRNA was observed in both cal-27 and SCC-9 cells after treatment with 5-AZA-2′-deoxycytidine (5-AZA-CdR). We demonstrated that knockdown of SPANXA1/A2 obviously inhibited tumor cell migration and invasion through EMT suppression. DNA hypomethylation might be responsible for the aberrant SPANXA1/A2 overexpressing. SPANXA1/A2 may be used as a diagnosed and independent prognosis indicator of HNSCC, and knockdown of SPANXA1/A2 may present a new gene-based therapy for HNSCC.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31472054, No. 81974297) and the National Key Research and Development Program of China (2016YFC1000600).

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Authors and Affiliations

  1. Department of Burn and Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China

    Jingjing Li & Shaorong Lei

  2. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, 172 Tongzipo Road, Changsha, 410013, China

    Hao Bo, Fang Zhu & Liqing Fan

  3. Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China

    Hao Bo & Liqing Fan

  4. College of Biotechnology, Guilin Medical University, Guilin, Guangxi, China

    Qiaohua Li & Tingwei Chen

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  1. Jingjing Li
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  2. Hao Bo
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  3. Fang Zhu
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  4. Qiaohua Li
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  5. Tingwei Chen
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  6. Shaorong Lei
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Correspondence to Shaorong Lei or Liqing Fan.

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Li, J., Bo, H., Zhu, F. et al. Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma. Med Oncol 37, 112 (2020). https://doi.org/10.1007/s12032-020-01441-2

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  • DOI: https://doi.org/10.1007/s12032-020-01441-2

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