Overexpression of long non-coding RNA HOTTIP increases chemoresistance of osteosarcoma cell by activating the Wnt/β-catenin pathway.

Abstract

Long non-coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors that are involved in tumorigenesis and chemotherapy resistance. HOTTIP is located at the 5' tip of the HOXA locus and coordinates the activation of multiple 5' HOXA genes, which plays an important role in multiple cancers. However, its biological role in the development of the chemoresistance phenotype of osteosarcoma (OS) is still unknown. In this study, we explored the roles of lncRNA HOTTIP in the initiation and chemoresistance of OS. We found that HOTTIP was increased in OS and up-regulated expression of HOTTIP could promoted OS cell proliferation and cell cycle progression by activating the Wnt/β-catenin pathway. Down-regulated expression of HOTTIP inhibited cell proliferation and arrested cell cycle at G1 phase by inhibition of Wnt/β-catenin pathway. Furthermore, our data showed that increased expression of HOTTIP was correlated with chemoresistance in OS. In vitro, HOTTIP induced cellular resistance to cisplatin by activating the Wnt/β-catenin pathway, which could be reversed by treatment with the Wnt/β-catenin inhibitor. Taken together, these findings indicated that HOTTIP play a pivotal role in OS cell initiation and chemoresistance via activating Wnt/β-catenin signaling pathway, which suggested potential use of HOTTIP for the treatment of osteosarcoma.