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miR-21 Induces Chemoresistance in Ovarian Cancer Cells via Mediating the Expression and Interaction of CD44v6 and P-gp

Authors Wang Y, Chen G, Dai F, Zhang L, Yuan M, Yang D, Liu S, Cheng Y

Received 17 October 2020

Accepted for publication 9 December 2020

Published 12 January 2021 Volume 2021:14 Pages 325—336

DOI https://doi.org/10.2147/OTT.S286639

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Yanqing Wang,1,* Gantao Chen,2,* Fangfang Dai,1 Li Zhang,1 Mengqin Yuan,1 Dongyong Yang,1 Shiyi Liu,1 Yanxiang Cheng1

1Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 2Department of Gastroenterology, Third People’s Hospital of Xiantao in Hubei Province, Wuhan 433000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yanxiang Cheng
Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuhan, Hubei 430060, People’s Republic of China
Email yanxiangCheng@whu.edu.cn

Background: Ovarian cancer (OC), a representative female reproductive system tumor, is one of the most malignant tumors in female. The most important reason for its poor prognosis is because of its high rate of chemotherapy resistance.
Results: This study aims to explore the effects of miR-21 on the chemotherapy resistance of OC cells. The functions of miR-21 on proliferation, migration and invasion of OC cells were assessed by transwell, clonal formation and CCK8 assay. Expression levels of miR-21, P-gp and CD44v6 in SKOV3 (cisplatin sensitive) cells and SKOV3/DDP (cisplatin resistant) cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Si-CD44v6 was transfected into OC cells to detect the influence on P-glycoprotein (P-gp) expression. Immunofluorescence was used to detect the localization of CD44v6 and P-gp in cell. Co-immunoprecipitation was used to detect the relationship between CD44v6 and P-gp. Results showed that miR-21 expression in cisplatin-resistant SKOV3/DDP cells was significantly higher than that in SKOV3 cells, at the same time, cells proliferation, as well as invasion and migration ability were enhanced after the miR-21 mimics transfected into SKOV3 cisplatin-sensitive cells. Furthermore, miR-21 expression level affected the CD44v6 and P-gp expression. Immunofluorescence and co-immunoprecipitation showed that CD44v6 and P-gp protein could interact.
Conclusion: In conclusion, the high miR-21 expression level could increase the proliferation, invasion, and migration ability of OC cells. And the interaction of CD44v6 and P-gp may mediate miR-21 involvement in chemotherapy resistance of OC cells.

Keywords: ovarian cancer, chemotherapy resistance, CD44v6, P-glycoprotein

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