Methylated Tumor Suppressor Gene SCARA5 Inhibits the Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma

Abstract

Background: SCARA5 may play an important role in nasopharyngeal carcinoma. Materials & methods: PCR and immunohistochemistry were used to detect the expression and promoter methylation of SCARA5. Cell proliferation assays, spheroid culture, flow cytometry analysis, Transwell assays and xenotransplantation tests were utilized to determine the functional effects of SCARA5. RNA-sequencing, western blotting, immunofluorescence and dual-luciferase reporter assays were used to assess SCARA5-mediated outcomes. Results:SCARA5 was downregulated by promoter methylation. Overexpression of SCARA5 inhibited cell migration, invasion and proliferation. SCARA5 enhanced nasopharyngeal carcinoma cell sensitivity to chemotherapy with cisplatin and 5-fluorouracil. SCARA5 drives tumor apoptosis by downregulating HSPA2. Conclusion:SCARA5 may be a useful clinical marker in nasopharyngeal carcinoma.

Tweetable abstract

Promoter methylation suppressed SCARA5 translation in nasopharyngeal carcinoma (NPC). SCARA5 suppressed NPC cell proliferation by promoting G0/G1 phase arrest and cell apoptosis by suppressing HSPA2 expression. Meanwhile, SCARA5 suppressed sphere-forming capacity, migration and invasion of NPC cells.

Keywords::

• apoptosis
• caspase 3
• HSPA2
• methylation
• nasopharyngeal carcinoma
• SCARA5

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0154

Author Contributions

T Xiang, P Ji, Y Yang: conception and design; X Jiang, Y Jiang: performed majority of experiments; Y Jiang: performed experiments and analyzed data; D An, X Jiang, Y Liu, S Zhou: collected samples; X Jiang, Y Jiang, R Tian, Z Li: drafted the manuscript; T Xiang, P Ji, Y Yang: reviewed data and the manuscript; T Xiang, P Ji, Y Yang: reviewed data and finalized the manuscript. All authors reviewed and approved the final version.

Acknowledgements

The authors would like to thank the staff of the Department of Otorhinolaryngology and the Key Laboratory of Molecular Oncology and Epigenetics for their help in sample collection and technical assistance.

Financial & competing interests disclosure

This study was supported by National Natural Science Foundation of China (#81970864), Natural Science Foundation of Chongqing (cstc2018jscx-mszdX0039), Chongqing Health and Family Planning Commission Research Project (2015HBRC004), Chongqing Middle and Youth Medical High-end Talent Studio Project (Yu Wei [2018] no. 2) and Chongqing Talent Project (cstc2021ycjh-bgzxm0080). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval by the Animal Ethics Committee of the Experimental Animal Center of the Chongqing Medical University, Chongqing, China (#IACUC-CQMU-2023-0172). All protocols concerning the use of patient samples in this study were approved by the Institutional Ethics Committees of The First Affiliated Hospital of Chongqing Medical University (2019-326#).

Additional information

Funding

This study was supported by National Natural Science Foundation of China (#81970864), Natural Science Foundation of Chongqing (cstc2018jscx-mszdX0039), Chongqing Health and Family Planning Commission Research Project (2015HBRC004), Chongqing Middle and Youth Medical High-end Talent Studio Project (Yu Wei [2018] no. 2) and Chongqing Talent Project (cstc2021ycjh-bgzxm0080). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.