Recently, the role of lncRNAs in
tumorigenesis and development has received increasing attention, but the mechanism underlying lncRNAs-mediated
tumor growth in the hypoxic microenvironment of solid
tumors remains obscure. Using
RNA sequencing, 25
hypoxia-related lncRNAs were found to be upregulated in HCC, of which
lncRNA USP2-AS1 were significantly increased under
hypoxia. We further confirmed that USP2-AS1 was significantly upregulated in
liver cancer using FISH assay and that USP2-AS1 was associated with advanced
liver cancer and increased
tumor size. Furthermore, overexpression of USP2-AS1 under
hypoxia dramatically increased HCC proliferation and clone formation, whereas the opposite results were observed after USP2-AS1 knockdown. We also found that overexpression of USP2-AS1 increased migration and invasion of HCC cells, while USP2-AS1 knockdown led to the opposite effect. In addition, USP2-AS1 knockdown can increase the efficacy of
lenvatinib in our mice
tumor xenograft model. Our findings also suggest that USP2-AS1 could increase the
protein level of HIF1α by enhancing YBX1 protein binding to HIF1α
mRNA under
hypoxia and the
therapeutic effect of
lenvatinib can be enhanced by combination with HIF1α inhibitors in
liver cancer.