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

被引:40
作者
Yan, Pei [1 ]
Su, Zijie [1 ]
Zhang, Zhenhua [1 ]
Gao, Teng [1 ]
机构
[1] Henan Prov Peoples Hosp, Dept Thyroid Surg, 7 Weiwu Rd, Zhengzhou 450000, Henan, Peoples R China
关键词
anaplastic thyroid carcinoma; nuclear paraspeckle assembly transcript 1; microRNA-9-5p; sperm-associated antigen 9; cisplatin resistance; TESTIS ANTIGEN SPAG9; BREAST-CANCER; PROMOTES; PROLIFERATION; PROGRESSION; MICRORNA-9; OVEREXPRESSION; PROGNOSIS; CERNA;
D O I
10.3892/ijo.2019.4868
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:988 / 1002
页数:15
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