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The purpose of this study is to elucidate the roles and potential underlying mechanisms of long noncoding RNA lnc-ZNF281 in glioma. We performed qRT-PCR to detect the expression levels of lnc-ZNF281 in glioma tissues. The effects of lnc-ZNF281 on the proliferative and migrative abilities of T98G and HS683 glioma cells were examined by cell proliferation assay, colony formation assay, wound-healing assay, and transwell assay. Also, the effects of lnc-ZNF281 on AKT/GSK-3 β / β -catenin pathway were analyzed. The results showed that the expression of lnc-ZNF281 in glioma tissues was decreased compared with normal tissues. lnc-ZNF281 overexpression inhibited the proliferative and migrative abilities of glioma cells, while lnc-ZNF281 knockdown obtained the opposite findings. Besides, overexpression of lnc-ZNF281 in glioma cells inactivated the AKT/GSK-3 β / β -catenin signaling pathway. Furthermore, β -catenin activation reversed the suppressive effects of lnc-ZNF281 on glioma cells. Taken together, lnc-ZNF281 inhibits glioma cell proliferation and migration via AKT/GSK-3 β / β -catenin pathway and may serve as a potential target for glioma treatment., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Yu-Qin Deng et al.)