LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR‑9‑5p and regulating SPAG9 expression

Yan,Pei; Su,Zijie; Zhang,Zhenhua; Gao,Teng

doi:10.3892/ijo.2019.4868

LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR‑9‑5p and regulating SPAG9 expression

Authors:
- Pei Yan
- Zijie Su
- Zhenhua Zhang
- Teng Gao
View Affiliations

Affiliations: Department of Thyroid Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China
Published online on: September 4, 2019 https://doi.org/10.3892/ijo.2019.4868
Pages: 988-1002
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its resistance to all conventional treatments. The long non‑coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) serves a critical role in cancer chemoresistance; however, whether NEAT1 is associated with chemoresistance of ATC remains unclear. In the present study, reverse transcription‑quantitative PCR assays were performed to detect the expression levels of NEAT1, microRNA (miR)‑9‑5p and sperm‑associated antigen 9 (SPAG9). Western blot analysis was conducted to assess the protein expression levels of p62, microtubule‑associated proteins 1A/1B light chain 3B and SPAG9. Cell proliferation was detected using the Cell Counting kit‑8 assay, and cell apoptosis was determined by flow cytometry. Dual‑luciferase reporter and RNA immunoprecipitation assays were performed to verify the interaction between NEAT1 and miR‑9‑5p, or miR‑9‑5p and SPAG9. Furthermore, an animal model was used to investigate the regulatory effects of NEAT1 on cisplatin (DDP)‑resistance in tumors in vivo. The present results demonstrated that NEAT1 was upregulated in ATC tissues and cell lines, and NEAT1 silencing resulted in decreased DDP‑resistance of ATC cells. In addition, NEAT1 suppressed miR‑9‑5p expression by binding to miR‑9‑5p and SPAG9 was a direct target of miR‑9‑5p. miR‑9‑5p overexpression sensitized ATC cells to DDP. Notably, NEAT1 silencing exerted its inhibitory effect on DDP‑resistance of ATC via the miR‑9‑5p/SPAG9 axis in vitro and in vivo. In conclusion, the present study demonstrated that NEAT1 silencing ameliorated DDP‑resistance of ATC, at least in part by reducing miR‑9‑5p sponging and regulating SPAG5 expression; therefore, NEAT1 may be considered a potential therapeutic target of ATC.

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