Cancer Management and Research (Mar 2020)
LncRNA EMX2OS Induces Proliferation, Invasion and Sphere Formation of Ovarian Cancer Cells via Regulating the miR-654-3p/AKT3/PD-L1 Axis
Abstract
Meng Duan,* Meixia Fang,* Changhe Wang, Hongyan Wang, Meng Li Department of Gynecology, Jining No. 1 People’s Hospital, Jining, Shandong 272000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng LiDepartment of Gynecology, Jining No. 1 People’s Hospital, Jining, Shandong 272000, People’s Republic of ChinaTel +86 537 2253304Email [email protected]: Long noncoding RNA (lncRNA) deregulation is frequent in human ovarian cancers (OCs), but the role of specific miRNAs involved in this disease remains elusive. LncRNA EMX2OS was previously reported to act as an oncogene in human cancers. However, their accurate expression, function and underlying mechanisms in OC are largely unclear.Materials and Methods: The levels of EMX2OS in OC tissues and cell lines were determined by quantitative real-time PCR, and the function of EMX2OS was then analyzed both in vitro and in vivo. Luciferase assays and immunoprecipitation assays were performed to analyze the association between EMX2OS and miR-654 expression in OC cells.Results: EMX2OS is overexpressed in human ovarian cancer tissues. Knockdown of EMX2OS reduced, while overexpression of EMX2OS enhanced the proliferation, invasion and sphere formation of OC cells. In addition, EMX2OS enhanced tumor growth in an in vivo xenograft model of human OC. We discovered that EMX2OS directly binds to miR-654 and suppresses its expression, thus leading to the upregulation of AKT3, which served as a direct target of miR-654. Moreover, miR-654 inhibited cell proliferation, invasion and sphere formation, and restoration of AKT3 reversed the effects of EMX2OS silencing or miR-654 overexpression. Furthermore, PD-L1 was identified as the key oncogenic component acting downstream of AKT3 in OC cells. Ectopic expression of PD-L1 reversed the anti-cancer functions by EMX2OS knockdown, AKT3 silencing or miR-654 upregulation in OC cells.Conclusion: These results demonstrated that the EMX2OS/miR-654/AKT3/PD-L1 axis confers aggressiveness in ovarian cancer and may represent a therapeutic target for OC metastasis.Keywords: EMX2OS, ovarian cancer, AKT3, microRNA-654, PD-L1
