Abstract
Background
MiR-4497 has been previously proved to exert an anti-cancer role in laryngeal squamous cell carcinoma (LSCC) by negatively regulating gastrulation brain homeobox 2 (GBX2). However, the mechanism of miR-4497 in LSCC has yet to be fully elucidated. This study intended to investigate the role of FEZF1-AS1 in the migration and invasion of LSCC cells and clarified its mechanism through miR-4497 and GBX2.
Methods
qPCR evaluated the expression of FEZF1-AS1, miR-4497 and GBX2 in LSCC tissues and cells, compared with controls. Western blotting analyzed GBX2, E-cadherin, N-cadherin and Vimentin. CCK8, wound healing and transwell assays assessed the viability, migration and invasion of TU686 and UM-SCC-17A cells. Luciferase reporter assay affirmed the interplay of miR-4497 with FEZF1-AS1 or GBX2 and Pearson’s correlation analysis explored the association between each two genes in both tumor and non-tumor tissues.
Results
FEZF1-AS1 was highly expressed in LSCC tissues and cells. Silence or elevation of FEZF1-AS1 inhibited or promoted the migration and invasion of TU686 and UM-SCC-17A cells. FEZF1-AS1 targeted and negatively modulated miR-4497. Inhibition of miR-4497 markedly restored the FEZF1-AS1 silence-repressed cell viability of TU686 and UM-SCC-17A cells. Further, FEZF1-AS1 could positively regulate GBX2 via negative regulation of miR-4497. In these two cells, GBX2 deficiency reversed the promoting impacts of miR-4497 repression on migration and invasion.
Conclusion
Taken together, FEZF1-AS1, heightened in LSCC tissues and cells, promotes cell migration and invasion of LSCC cells via targeting miR-4497 that inhibits GBX2. The finding may offer new options for the treatment of this cancer.
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Availability of data and materials
The analysed data sets generated during the study are available from the corresponding author on reasonable request.
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This work was supported by the Medical and Health Project of Zhejiang Province [2020360873].
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Substantial contributions to conception and design: XDC. Data acquisition, data analysis and interpretation: PC, CHH. Drafting the article or critically revising it for important intellectual content: XDC. Final approval of the version to be published: all authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: all authors.
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Forty cancerous tissues and adjacent non-tumor tissues were gained from patients diagnosed as laryngeal squamous cell carcinoma between July 2018 and October 2019 in First Hospital of Ningbo City. After section, tissues were frozen and stored at − 80 °C. Each patient signed written informed consent. This study was approved by the Ethics Committee of First Hospital of Ningbo City and experimental procedures were in accordance with the Declaration of Helsinki Principles.
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Chen, X., Cheng, P. & Hu, C. LncRNA FEZF1-AS1 accelerates the migration and invasion of laryngeal squamous cell carcinoma cells through miR-4497 targeting GBX2. Eur Arch Otorhinolaryngol 278, 1523–1535 (2021). https://doi.org/10.1007/s00405-021-06636-5
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DOI: https://doi.org/10.1007/s00405-021-06636-5