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ZFAS1 Promotes Cisplatin Resistance via Suppressing miR-421 Expression in Oral Squamous Cell Carcinoma

Authors Wang X, Hao R, Wang F, Wang F

Received 8 February 2020

Accepted for publication 3 April 2020

Published 13 August 2020 Volume 2020:12 Pages 7251—7262


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly

Xiaolong Wang,1,* Rui Hao,2,* Fengjuan Wang,1 Fan Wang1

1Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People’s Repubic of China; 2Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People’s Repubic of China

*These authors contributed equally to this work

Correspondence: Fengjuan Wang Email
Fan Wang Email

Purpose: Oral squamous cell carcinoma (OSCC), with high incidence and mortality, represents one of the main reasons for head and neck malignant tumors. We want to investigate the effect of ZFAS1 on DDP resistance in oral squamous cell carcinoma.
Methods: The proliferation and migration of cells was detected by CCK-8 and Transwell assay. The apoptosis was measured by flow cytometry and Western blot. The interaction of ZFAS1, miR-421, and MEIS2 was verified by luciferase reporter assay. The role of ZFAS1 in DDP resistance in vivo was tested by the nude mice model. The expression of ZFAS1 in exosomes from cisplatin-resistant patients was also determined.
Results: ZFAS1 overexpression improved OSCC cell growth and inhibited OSCC cell susceptibility to DDP. In addition, the silencing of ZFAS1 promoted DDP-induced apoptosis. ZFAS1 directly bound to miR-421, which was verified by luciferase reporter assay. Inhibition of miR-421 reversed the effect of si-ZFAS1, which promoted the cell viability and decreased the sensitivity of DDP in DDP-resistant cells. The in vivo experiment showed the role of ZFAS1 in increasing the DDP resistance in OSCC tumor. Importantly, this study also showed upregulated ZFAS1 in serum exosomes derived from cisplatin-resistant patients.
Conclusion: ZFAS1 promotes chemoresistance of oral squamous cell carcinoma to cisplatin and might become a latent therapeutic target for treating OSCC.

Keywords: chemoresistance, cisplatin, oral squamous cell carcinoma, ZFAS1, miR-421, exosome

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