Cancer Management and Research (Aug 2020)
NEAT1 Knockdown Suppresses the Cisplatin Resistance in Ovarian Cancer by Regulating miR-770-5p/PARP1 Axis
Abstract
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 workCorrespondence: Xin Wang Tel +86- 23-79335226Email [email protected]: 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
