Furthermore, our results indicate that HIF-1α, as a transcript factor, could directly bind to the MAPKAPK5-AS1 promoter to activate its transcription, and MAPKAPK5-AS1 regulates HIF-1α expression through PLAGL2 to form a hypoxia-mediated MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC. This evidence concerns the gene HIF1A and hepatocellular carcinoma.