Long Noncoding RNA Expression Profiling Reveals Upregulation of Uroplakin 1A and Uroplakin 1A Antisense RNA 1 under Hypoxic Conditions in Lung Cancer Cells.

Hypoxia plays important roles in cancer progression by inducing angiogenesis, metastasis, and drug resistance. However, the effects of hypoxia on long noncoding RNA (lncRNA) expression have not been clarified. Herein, we evaluated alterations in lncRNA expression in lung cancer cells under hypoxic conditions using lncRNA microarray analyses. Among 40,173 lncRNAs, 211 and 113 lncRNAs were up- and downregulated, respectively, in both A549 and NCI-H460 cells. Uroplakin 1A () and -antisense RNA 1 (), which showed the highest upregulation under hypoxic conditions, were selected to investigate the effects of on the expression of and the mechanisms of hypoxia-inducible expression. Following transfection of cells with small interfering RNA (siRNA) targeting hypoxiainducible factor 1α (HIF-1α), the hypoxia-induced expression of and - was significantly reduced, indicating that HIF-1α played important roles in the hypoxiainduced expression of these targets. After transfection of cells with siRNA, and - levels were reduced. Moreover, transfection of cells with - siRNA downregulated both - and . RNase protection assays demonstrated that and - formed a duplex; thus, transfection with - siRNA decreased the RNA stability of . Overall, these results indicated that and - expression increased under hypoxic conditions in a HIF-1α-dependent manner and that formation of a /- duplex affected RNA stability, enabling each molecule to regulate the expression of the other.