The differential expression of genes in HepG2 cells caused by UC001kfo RNAi was investigated using RNA-seq.HepG2 cells were infected by Lenti-shUC001kfo lentivirus particles.The expression of UC001kfo mRNA in the HepG2-shUC001kfo cell line was detected by real-time PCR.RNA-seq technology was used to identify the difference in the expression of genes regulated by lncRNA UC001kfo in the HepG2 cell line.Gene ontology and signaling pathway analysis were performed to reveal the biological functions of the genes encoding of significantly different mRNAs.The results showed that mRNAs were differentially expressed between the HepG2-shUC001kfo cell line and the HepG2 cell line.The UC001kfo mRNA was significantly down-regulated in the stable cell line HepG2-shUC001kfo (P＜0.001).Additionally,we found 19 signaling pathways or functional classifications encompassing 30 genes that played a role in cancer characteristics,cell adhesion,invasion and migration.The results also showed that the expression of many genes associated with cancer cell invasion and metastasis was decreased with the down-regulation of the lncRNA UC001kfo.LncRNA UC001kfo may play a role in regulating cancer cell invasion and metastasis.It was suggested that mRNAs were differentially expressed in the HepG2 cell line after the down-regulation of lncRNA-UC001kfo.Some took part in the extracellular matrix,cell adhesion,motility,growth,and localization.The genes encoding of differentially expressed mRNAs may participate in cell invasion and metastasis.