HIF-1α-induced upregulation of lncRNA UCA1 promotes cell growth in osteosarcoma by inactivating the PTEN/AKT signaling pathway

Increasing evidence indicates that long non-coding RNAs (lncRNAs) play an important role in multiple biological processes including cell growth, differentiation, proliferation and invasion. Urothelial carcinoma associated 1 (UCA1) is a highly conserved nuclear ncRNA and a key regulator of cell proliferation and apoptosis in several types of cancers. However, its role in osteosarcoma progression is not well known. In the present study, we aimed to determine the biological role of UCA1 in osteosarcoma progression. RT-qPCR analysis showed that UCA1 expression was significantly increased in osteosarcoma cell lines and promoted cell growth in osteosarcoma. We then sought to determine the mechanism underlying the upregulation of UCA1 in osteosarcoma. Luciferase reporter assay and chromatin immunoprecipitation assay suggested that lncRNA UCA1 was induced by HIF-1 alpha and HIF-1 alpha interacts with the HIF-1 alpha response element in the promoter region of UCA1. In addition, the gain- and loss-of-functional assay showed that HIF-1 alpha promoted osteosarcoma cell growth through inducing the UCA1 expression level. More importantly, Cignal Signal Transduction Reporter Array and western blot assay showed that lncRNA UCA1 inactivated the PTEN/AKT signaling pathway. Finally, we observed that HIF-1 alpha induced cell growth through the UCA1/PTEN/AKT signaling pathway. To conclude, our integrated approach demonstrates that UCA1 confers a tumor promoter function by promoting cell proliferation and silencing of the PTEN/AKT signaling pathway in osteosarcoma. Thus, UCA1 can serve as a promising therapeutic target for osteosarcoma patients.