Long noncoding RNA ZEB1-AS1 acts as an oncogene in osteosarcoma by epigenetically activating ZEB1.

Abstract

Long noncoding RNAs (lncRNAs) have been demonstrated to be dysregulated in many disease states and have pivotal roles in various pathophysiological processes. However, the expression, roles and potential mechanism of lncRNA ZEB1-AS1 in osteosarcoma are still unknown. In this study, we measured ZEB1-AS1 expression and the results showed that ZEB1-AS1 was upregulated in osteosarcoma tissues and cells. Increased expression of ZEB1-AS1 is correlated with larger tumor size, progressed Enneking stage, tumor metastasis, worse recurrence-free and overall survival of osteosarcoma patients. Functional experiments showed that enhanced expression of ZEB1-AS1 promotes osteosarcoma cells proliferation and migration. By contrast, ZEB1-AS1 knockdown inhibits osteosarcoma cells proliferation and migration. Mechanistically, ZEB1-AS1 directly binds and recruits p300 to the <i>ZEB1</i> promoter region, induces an open chromatin structure, and activates <i>ZEB1</i> transcription. There is a significant correlation between the expression of ZEB1-AS1 and ZEB1 in osteosarcoma tissues. ZEB1 depletion abrogates the roles of ZEB1-AS1 on the proliferation and migration of osteosarcoma cells. Collectively, these findings demonstrated that ZEB1-AS1 functions as an oncogene in osteosarcoma via epigenetically activating ZEB1 and could be a potential target for osteosarcoma treatment.