Recently, long noncoding RNAs (lncRNAs) were found to be dysregulated in a 
variety of tumors. However, it remains unknown how and through what molecular 
mechanisms the expression of lncRNAs is controlled. In this study, we found that 
the lncRNA Low Expression in Tumor (lncRNA-LET) was generally downregulated in 
hepatocellular carcinomas, colorectal cancers, and squamous-cell lung 
carcinomas. We demonstrated that hypoxia-induced histone deacetylase 3 repressed 
lncRNA-LET by reducing the histone acetylation-mediated modulation of the 
lncRNA-LET promoter region. Interestingly, the downregulation of lncRNA-LET was 
found to be a key step in the stabilization of nuclear factor 90 protein, which 
leads to hypoxia-induced cancer cell invasion. Moreover, the relationship among 
hypoxia, histone acetylation disorder, low lncRNA-LET expression level, and 
metastasis was found in clinical hepatocellular carcinoma samples. These results 
advance our understanding of the role of lncRNA-LET as a regulator of hypoxia 
signaling and offer new avenues for therapeutic intervention against cancer 
progression.