MicroRNA-101-3p inhibits nasopharyngeal carcinoma cell proliferation and cisplatin resistance through ZIC5 down-regulation by targeting SOX2

Tieqi Li; Gehou Zhang; Wei Li; Jian Xiao; Zheng Zhou; Guolin Tan; Jingang Ai

doi:10.1515/hsz-2022-0329

Article

MicroRNA-101-3p inhibits nasopharyngeal carcinoma cell proliferation and cisplatin resistance through ZIC5 down-regulation by targeting SOX2

Tieqi Li , Gehou Zhang , Wei Li , Jian Xiao , Zheng Zhou , Guolin Tan and Jingang Ai

Published/Copyright: February 9, 2023

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From the journal Biological Chemistry Volume 404 Issue 10

Abstract

This study aims to explore the mechanism of microRNA (miR)-101-3p-mediated SOX2/ZIC5 axis in the progression of cisplatin resistance of nasopharyngeal carcinoma (NPC). ZIC5 expression was analyzed with a bioinformatics database and detected in NPC cell lines. Cisplatin-resistant cells (HNE-1/DDP and C666-1/DDP) were transfected with sh-ZIC5, sh-SOX2, sh-SOX2 + pcDNA3.1-ZIC5, or miR-101-3p Agomir + pcDNA3.1-SOX2. MiR-101-3p, SOX2, and ZIC5 expression was assessed after transfection, and cancer associated phenotypes were evaluated after cisplatin treatment. The potential relationships among miR-101-3p, SOX2, and ZIC5 were analyzed. A xenograft mouse model of NPC was established with HNE-1 cells stably transfected or not transfected with oe-ZIC5 and subjected to tail vein injection of miR-101-3p Agomir and intraperitoneal injection of cisplatin. Overexpression of ZIC5 was found in cisplatin-resistant NPC cells. Downregulating ZIC5 in NPC cells decreased cell viability, promoted apoptosis, and reduced cisplatin resistance. SOX2 had a binding site on ZIC5, and SOX2 promoted proliferation, migration, and cisplatin resistance and inhibited cell apoptosis by up-regulating ZIC5. Mechanistically, miR-101-3p was decreased in cisplatin-resistant NPC cells and negatively targeted SOX2. Overexpression of miR-101-3p inhibited tumor growth and cisplatin resistance in xenograft mouse model, which was reversed by ZIC5 overexpression. In conclusion, the miR-101-3p/SOX2/ZIC5 axis was implicated in cancer associated phenotypes and cisplatin resistance in NPC.

Keywords: cisplatin resistance; microRNA-101-3p; nasopharyngeal carcinoma; proliferation; SOX2; ZIC5

Corresponding author: Jingang Ai, Department of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Rd, Changsha 410013, Hunan, P. R. China, E-mail: ajg2014@csu.edu.cn

Tieqi Li and Gehou Zhang contributed equally to this work.

Funding source: Natural Science Foundation of Hunan Province

Award Identifier / Grant number: 2021JJ40913

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81902785

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Dr Jingang Ai was supported by the National Natural Science Foundation of China (No.81902785) and the Natural Science Foundation of Hunan Province (No.2021JJ40913).
Conflict of interest statement: The authors declare there is no conflict of interest regarding the publication of this paper.

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Received: 2022-11-17

Accepted: 2023-01-25

Published Online: 2023-02-09

Published in Print: 2023-09-26

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Articles in the same Issue

https://doi.org/10.1515/hsz-2022-0329

Keywords for this article

cisplatin resistance; microRNA-101-3p; nasopharyngeal carcinoma; proliferation; SOX2; ZIC5