LAUSR

In our previous study, we found long noncoding RNA ZEB1‐AS1 is upregulated and functions as an oncogene in osteosarcoma. MiR‐200 family (miR‐200s) functions as tumor suppressor via directly targeting ZEB1 in various cancers. In this study, we further investigate the potential interplay between ZEB1‐AS1, miR‐200s, and ZEB1 in osteosarcoma. Our results showed that ZEB1‐AS1 functions as a molecular sponge for miR‐200s and relieves the inhibition of ZEB1 caused by miR‐200s. ZEB1‐AS1 and miR‐200s reciprocally negatively regulate each other. MiR‐200s are downregulated in osteosarcoma tissues, and negatively correlated with ZEB1‐AS1 and ZEB1 expression levels in osteosarcoma. Functional experiments showed that consistent with ZEB1‐AS1 depletion, miR‐200s overexpression and ZEB1 depletion both inhibit osteosarcoma cell proliferation and migration. Overexpression of miR‐200s partially abolished the effects of ZEB1‐AS1 on osteosarcoma cell proliferation and migration. Moreover, the combination of ZEB1‐AS1 depletion and miR‐200s overexpression significantly inhibits osteosarcoma cell proliferation and migration. In conclusion, this study revealed a novel regulatory mechanism between ZEB1‐AS1, miR‐200s, and ZEB1. The interplay between ZEB1‐AS1 and miR‐200s contributes to osteosarcoma cell proliferation and migration, and targeting this interplay could be a promising strategy for osteosarcoma treatment. J. Cell. Biochem. 118: 2250–2260, 2017. © 2017 Wiley Periodicals, Inc.