OBSTETRICS AND GYNAECOLOGY / RESEARCH PAPER
Long non-coding RNA NEAT1/miR-320b/MSI2 axis regulates cisplatin resistance in ovarian cancer
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1
Department of Pharmacy, Eye, Ear, Nose and Larynx Hospital, Liaocheng People's Hospital, Liaocheng, Shandong, China., China
2
Department of Pharmacy, Eye, Ear, Nose and Larynx Hospital, Liaocheng People's Hospital, No.Dongchang West Road 252000, Liaocheng, Shandong, China., China
Submission date: 2020-01-10
Final revision date: 2020-12-10
Acceptance date: 2020-12-10
Online publication date: 2021-04-05
Corresponding author
Degang Zhou
Department of Pharmacy, Eye, Ear, Nose and Larynx Hospital, Liaocheng People's Hospital, No.Dongchang West Road 252000, Liaocheng, Shandong, China., China
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ABSTRACT
Introduction:
Ovarian cancer (OC) frequently occurs in postmenopausal women and it has higher mortality rate. Accumulating researches proved that long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) involved in the progression of chemoresistance in human OC. Here, the study aimed to investigate the partial molecular mechanism of OC chemoresistance.
Material and methods:
The levels of NEAT1 and microRNA-320b (miR-320b) were measured by qRT-PCR. Western blot was carried out to determine the protein levels that used in this research. Cell viability was identified via Cell Counting Kit-8 (CCK-8). Transwell assay was employed to determine migration and invasion. The relationship between miR-320b and NEAT1 or MSI2 was clarified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull down assay. Also, a murine xenograft assay was used to explore the effect of NEAT1 on cisplatin resistance in OC in vivo.
Results:
The level of NEAT1 was significantly increased in cisplatin resistant OC cell lines. Downregulation of NEAT1 enhanced cisplatin sensibility in OVCAR-3/DDP and HEY/DDP cells. Furthermore, miR-320b was a target of NEAT1, and the effects of knockdown of NEAT1 on the cell viability, IC50 of cisplatin, migration and invasion in OVCAR-3/DDP and HEY/DDP were restored by the inhibitor of miR-320. In addition, miR-320b directly targeted MSI2 to regulate cisplatin sensibility in cisplatin resistant OC cells. In addition, downregulation of NEAT1 decreased cisplatin resistance in OC in vivo.
Conclusions:
NEAT1 regulated cisplatin resistance through NEAT1/miR-320b/MSI2 axis in OC, which might offer a novel therapy target for the chemotherapy of OC.