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

Molecular Therapy: Nucleic Acids

Ying-Jia Li¹  Jin Chen²  Shou-Guo Huang²  Qing-Ping Wu²  Qiu Meng²  Xin-Rong Yu²  Hong Cheng²  Hong-Ye Yun²  Jing Zhang²  Jian-Tao Fu²  Hai-Yan Wang²  Li-Ni Quan²  Jie Wang²  Pin Yu² 

[1]Clinical Laboratory, Third Xiangya Hospital of Central South University, No. 138 Tong Zipo Road, Changsha 410013, Hunan Province, P.R. China

[2]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

关键词: ovarian cancer;    ZFAS1;    miR-548e;    CXCR4;    Let-7a;    metastasis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown