miR-548e Sponged by ZFAS1 Regulates Metastasis and Cisplatin Resistance of OC by Targeting CXCR4 and let-7a/BCL-XL/S Signaling Axis

Jing Zhang; Li-Ni Quan; Qiu Meng; Hai-Yan Wang; Jie Wang; Pin Yu; Jian-Tao Fu; Ying-Jia Li; Jin Chen; Hong Cheng; Qing-Ping Wu; Xin-Rong Yu; Hong-Ye Yun; Shou-Guo Huang

Molecular Therapy: Nucleic Acids (Jun 2020)

miR-548e Sponged by ZFAS1 Regulates Metastasis and Cisplatin Resistance of OC by Targeting CXCR4 and let-7a/BCL-XL/S Signaling Axis

Jing Zhang,
Li-Ni Quan,
Qiu Meng,
Hai-Yan Wang,
Jie Wang,
Pin Yu,
Jian-Tao Fu,
Ying-Jia Li,
Jin Chen,
Hong Cheng,
Qing-Ping Wu,
Xin-Rong Yu,
Hong-Ye Yun,
Shou-Guo Huang

Affiliations

Jing Zhang: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Li-Ni Quan: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Qiu Meng: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Hai-Yan Wang: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Jie Wang: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Pin Yu: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Jian-Tao Fu: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Ying-Jia Li: Clinical Laboratory, Third Xiangya Hospital of Central South University, No. 138 Tong Zipo Road, Changsha 410013, Hunan Province, P.R. China
Jin Chen: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Hong Cheng: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Qing-Ping Wu: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Xin-Rong Yu: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Hong-Ye Yun: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China
Shou-Guo Huang: Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China; Corresponding author: Shou-Guo Huang, Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43 Renmin Road, Haidian Island, Haikou 570208, Hainan Province, P.R. China.

Journal volume & issue: Vol. 20
pp. 621 – 638

Abstract

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Ovarian cancer (OC) is a severe malignancy featuring a poor prognosis due to rapid metastasis and chemotherapy resistance. In this study, we extensively investigated the upstream and downstream mechanisms of miR-548e in regulating OC progression and cisplatin resistance. Our results indicated that ZFAS1 was highly expressed and promoted OC cell proliferation, migration, invasion, and cisplatin resistance by directly suppressing miR-548e expression. ZFAS1 co-localized with miR-548e in the cytosols of OC cells. miR-548e repressed CXCR4 expression, and elevated CXCR4 expression promoted OC cell proliferation, migration, invasion, and cisplatin resistance. Cisplatin resistance induced by ZFAS1 and CXCR4 overexpression in OC cells was mediated by their suppression on let-7a and elevation of BCL-XL/S expression. ZFAS1 knockdown and miR-548e and let-7a overexpression impaired cisplatin resistance and suppressed lung metastatic nodule formation in nude mice. In conclusion, ZFAS1 binds with miR-548e to enhance CXCR4 expression to promote OC cell proliferation and metastasis, which also enhances cisplatin resistance by suppressing let-7a and elevating BCL-XL/S protein expression.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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