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 (UPK1A) and UPK1A-antisense
RNA 1 (AS1), which showed the highest upregulation under hypoxic conditions, were selected to investigate the effects of UPK1AAS1 on the expression of UPK1A 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 UPK1A and UPK1A-AS1 was significantly reduced, indicating that HIF-1α played important roles in the hypoxiainduced expression of these targets. After transfection of cells with UPK1A
siRNA, UPK1A and UPK1A-AS1 levels were reduced. Moreover, transfection of cells with UPK1A-AS1
siRNA downregulated both UPK1A-AS1 and UPK1A.
RNase protection assays demonstrated that UPK1A and UPK1A-AS1 formed a duplex; thus, transfection with UPK1A-AS1
siRNA decreased the RNA stability of UPK1A. Overall, these results indicated that UPK1A and UPK1A-AS1 expression increased under hypoxic conditions in a HIF-1α-dependent manner and that formation of a UPK1A/UPK1A-AS1 duplex affected RNA stability, enabling each molecule to regulate the expression of the other.