OncoTargets and Therapy (Nov 2020)
ZFAS1 Exerts an Oncogenic Role via Suppressing miR-647 in an m6A-Dependent Manner in Cervical Cancer
Abstract
Zhijuan Yang,1,* Jingwen Ma,1,* Shuxia Han,1 Xiaowen Li,1 Hua Guo,1 Dongtao Liu2 1Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia Province, People’s Republic of China; 2Gastrointestinal Department, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongtao LiuGastrointestinal Department, General Hospital of Ningxia Medical University, No. 804, Shengli South Street, Xingqing District, Yinchuan City, Ningxia Province 750004, People’s Republic of ChinaEmail [email protected]: Cervical cancer (CC) is the second serious health threat in women worldwide. LncRNA (ZNFX1 antisense RNA 1) ZFAS1 has been observed to abnormally express in human cancers. However, the expression pattern, clinical significance and molecular mechanism of ZFAS1 have not been thoroughly studied in CC.Methods: qRT-PCR was performed to examine the differential expression of ZFAS1 in CC tissues and adjacent normal cervical tissues. Gain- and loss-of-function experiments were constructed to test the functional role of ZFAS1 in CC by CCK-8, colony formation, transwell and xenograft models assays. Luciferase reporter, RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), RNA pull-down assays were used to reveal the underlying mechanisms.Results: We found that ZFAS1 was significantly upregulated in CC tissues. Elevation of ZFAS1 correlated with advanced FIGO stage, lymph node and distant metastasis, and also indicated poor overall survival in patients with CC. Functional experiments demonstrated that ZFAS1 promoted CC cell proliferation, migration and invasion in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistic investigation revealed that ZAFS1 sequestered miR-647, and this RNA–RNA interaction is regulated by METLL3-mediated m6A modification.Conclusion: Our findings elucidate the functional roles of ZFAS1 and its m6A modification in CC cells and indicate that ZFAS1 may be a promising target for CC treatment.Keywords: m6A modification, ceRNA, growth, metastasis
