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NEAT1 Knockdown Suppresses the Cisplatin Resistance in Ovarian Cancer by Regulating miR-770-5p/PARP1 Axis

Authors Zhu M, Yang L, Wang X

Received 7 April 2020

Accepted for publication 27 July 2020

Published 14 August 2020 Volume 2020:12 Pages 7277—7289

DOI https://doi.org/10.2147/CMAR.S257311

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Harikrishna Nakshatri


Mingzhe Zhu,1,* Lei Yang,2,* Xin Wang3

1Department of Obstetrics and Gynecology, Jilin Medical College Affiliated Hospital, Jilin City, Jilin Province 132011, People’s Republic of China; 2Department of Medical Clinic, Yuhuangding Hospital, Yantai City, Shandong Province 264000, People’s Republic of China; 3Department of Obstetrics, Qianjiang Central Hospital of Chongqing, Chongqing 409000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xin Wang Tel +86- 23-79335226
Email nbseqo@163.com

Background: Long noncoding RNAs play essential roles in regulating drug resistance in cancers. However, how and whether lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) could mediate cisplatin resistance in ovarian cancer remain poorly understood.
Patients and Methods: Eighteen cisplatin-sensitive and 19 cisplatin-resistant patients with ovarian cancer were recruited. Cisplatin-resistant ovarian cancer cells were used for this study. The expression levels of NEAT1, microRNA (miR)-770-5p and poly adenosine diphosphate-ribose polymerase 1 (PARP1) were detected by quantitative real-time polymerase chain reaction or Western blot. Cisplatin resistance was assessed by the half-maximal inhibitory concentration (IC50) of cisplatin, cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, flow cytometry and Western blot, respectively. The target association between miR-770-5p and NEAT1 or PARP1 was investigated by dual-luciferase reporter assay. The xenograft model was used to investigate cisplatin resistance in vivo.
Results: NEAT1 expression is elevated in cisplatin-resistant ovarian cancer tissues and cells. Knockdown of NEAT1 repressed cisplatin resistance by decreasing the IC50 of cisplatin, cell viability and increasing apoptosis. MiR-770-5p was bound to NEAT1 and PARP1 was confirmed as a target of miR-770-5p. MiR-770-5p inhibition or PARP1 restoration could abate the effect of NEAT1 silencing on cisplatin resistance in cisplatin-resistant ovarian cancer cells. Moreover, NEAT1 knockdown reduced PARP1 expression by increasing miR-770-5p. Interference of NEAT1 decreased xenograft tumor growth by regulating miR-770-5p and PARP1.
Conclusion: Knockdown of NEAT1 inhibited cisplatin resistance in ovarian cancer cells by up-regulating miR-770-5p and down-regulating PARP1, providing a new target for improving the efficacy of cisplatin-based therapy in ovarian cancer.

Keywords: ovarian cancer, cisplatin resistance, NEAT1, miR-770-5p, PARP1

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