Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma
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ORIGINAL PAPER
Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma Jingjing Li1 · Hao Bo2,3 · Fang Zhu2 · Qiaohua Li4 · Tingwei Chen4 · Shaorong Lei1 · Liqing Fan2,3 Received: 29 July 2020 / Accepted: 2 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords SPANXA1/A2 · Head and neck squamous cell carcinoma (HNSCC) · Migration and invasion · Epithelial– mesenchymal transition (EMT) · TCGA
Introduction
* Shaorong Lei [email protected] * Liqing Fan [email protected] 1
Department of Burn and Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China
2
Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, 172 Tongzipo Road, Changsha 410013, China
3
Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China
4
College of Biotechnology, Guilin Medical University, Guilin, Guangxi, China
Head and neck squamous cell carcinoma (HNSCC) continues to be an eighth leading cause of cancer with high metastasis and recurrence rates. Globally, up to 40% of patients with HNSCC develop local failure after anti-tumor treatment [1]. The prognosis of patients with the early stage is more favorable than that of patient
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