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
相关论文
共 43 条
[1]   p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity [J].
Adriaens, Carmen ;
Standaert, Laura ;
Barra, Jasmine ;
latil, MathilDe ;
Verfaillie, Annelien ;
Kalev, Peter ;
Boeckx, Bram ;
Wijnhoven, Paul W. G. ;
Radaelli, Enrico ;
Vermi, William ;
Leucci, Eleonora ;
Lapouge, Gaelle ;
Beck, Benjamin ;
van den Oord, Joost ;
Nakagawa, Shinichi ;
Hirose, Tetsuro ;
Sablina, Anna A. ;
Lambrechts, Diether ;
Aerts, Stein ;
Blanpain, Cedric ;
Marine, Jean-Christophe .
NATURE MEDICINE, 2016, 22 (08) :861-+
[2]   LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194 [J].
An, Jihong ;
Lv, Weiling ;
Zhang, Yongzhou .
ONCOTARGETS AND THERAPY, 2017, 10 :5377-5390
[3]   Autophagy: assays and artifacts [J].
Barth, Sandra ;
Glick, Danielle ;
Macleod, Kay F. .
JOURNAL OF PATHOLOGY, 2010, 221 (02) :117-124
[4]   The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer [J].
Chakravarty, Dimple ;
Sboner, Andrea ;
Nair, Sujit S. ;
Giannopoulou, Eugenia ;
Li, Ruohan ;
Hennig, Sven ;
Mosquera, Juan Miguel ;
Pauwels, Jonathan ;
Park, Kyung ;
Kossai, Myriam ;
MacDonald, Theresa Y. ;
Fontugne, Jacqueline ;
Erho, Nicholas ;
Vergara, Ismael A. ;
Ghadessi, Mercedeh ;
Davicioni, Elai ;
Jenkins, Robert B. ;
Palanisamy, Nallasivam ;
Chen, Zhengming ;
Nakagawa, Shinichi ;
Hirose, Tetsuro ;
Bander, Neil H. ;
Beltran, Himisha ;
Fox, Archa H. ;
Elemento, Olivier ;
Rubin, Mark A. .
NATURE COMMUNICATIONS, 2014, 5
[5]  
Chen XJ, 2015, AM J CANCER RES, V5, P2808
[6]  
Chen ZJ, 2016, EUR REV MED PHARMACO, V20, P3373
[7]   Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival [J].
Choudhry, H. ;
Albukhari, A. ;
Morotti, M. ;
Haider, S. ;
Moralli, D. ;
Smythies, J. ;
Schoedel, J. ;
Green, C. M. ;
Camps, C. ;
Buffa, F. ;
Ratcliffe, P. ;
Ragoussis, J. ;
Harris, A. L. ;
Mole, D. R. .
ONCOGENE, 2015, 34 (34) :4482-4490
[8]   Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia [J].
Gao, Caihua ;
Zhang, Jianying ;
Wang, Qingyan ;
Ren, Chunhua .
ONCOLOGY LETTERS, 2016, 12 (02) :1051-1057
[9]   Suppression of MicroRNA-9 by Mutant EGFR Signaling Upregulates FOXP1 to Enhance Glioblastoma Tumorigenicity [J].
Gomez, German G. ;
Volinia, Stefano ;
Croce, Carlo M. ;
Zanca, Ciro ;
Li, Ming ;
Emnett, Ryan ;
Gutmann, David H. ;
Brennan, Cameron W. ;
Furnari, Frank B. ;
Cavenee, Webster K. .
CANCER RESEARCH, 2014, 74 (05) :1429-1439
[10]   IncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer via Recruiting WDR5 [J].
Gu, Peng ;
Chen, Xu ;
Xie, Ruihui ;
Han, Jinli ;
Xie, Weibin ;
Wang, Bo ;
Dong, Wen ;
Chen, Changhao ;
Yang, Meihua ;
Jiang, Junyi ;
Chen, Ziyue ;
Huang, Jian ;
Lin, Tianxin .
MOLECULAR THERAPY, 2017, 25 (08) :1959-1973