LeXis gene therapy (University of California Los Angeles/Hughes Medical Institute)

Osteosarcoma (OS) is the most common primary bone cancer in adolescents and children. Long noncoding RNAs (lncRNAs) contain > 200 nucleotides and do not have protein-coding ability. Liver-expressed LXR-induced sequence (LeXis) is a newly identified functional lncRNA. However, its expression pattern, biological function, and molecular mechanism in OS progression are unclear. The present study is the first to show that LeXis expression was upregulated in OS tissues. Increased LeXis expression was significantly correlated with high tumor stage, large tumor size, and poor prognosis. Our findings highlight the oncogenic activity of lncRNA LeXis in OS growth. Results of functional assays showed that LeXis promoted OS growth both in vitro and in vivo. Mechanistic investigation showed that LeXis directly interacted with miR-199a and suppressed its expression. Moreover, LeXis increased CTNNB1 expression by functioning as a ceRNA of CTNNB1 against miR-199a. These findings may have important implications for developing novel therapeutic strategies for OS.