Background and aim: Long non-coding RNAs (lncRNAs) are implicated as novel factors in tumorigenesis and tumor progression. Although thousands of lncRNAs have been discovered, only a small portion have been functionally determined in hepatocellular carcinoma (HCC). Here, we aimed to comprehensively analyze differentially expressed lncRNAs, evaluate their clinical significance, and explore the functional roles and underlying mechanism in HCC.
Methods: We identified hundreds of lncRNAs which were dysregulated in HCC tissues through performing integrative analyses using the RNA sequencing data and independent gene microarray data from Gene Expression Omnibus and the Cancer Genome Atlas.
Results: Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients’ poor outcomes. Further experimental validation revealed that down-regulation of lncRNA DUXAP8 inhibited HCC cells proliferation and colony formation ability. Mechanistically, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with histone-lysine N-methyltransferase enzyme enhancer of zeste homolog 2.
Conclusion: Taken together, our findings can provide a valuable resource of HCC-associated lncRNAs and new insights into the biological functions of lncRNAs in HCC development.
Keywords: HCC, lncRNAs, DUXAP8, EZH2, KLF2