The Expression Profiling Of Long Non-coding RNA In Hepatocellular Carcinoma

Background Recently,growing evidence has suggested that long non-coding RNAs(lncRNAs)are capable of influencing multiple biological processes through various mechanisms as guides,scaffolds,and decoys.Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive malignancies worldwide,the study of which at the whole transcriptomic level,especially on the aspect of long non-coding RNAs,is still rather inadequate.Methods In this study,with the application of RNA high-throughput sequencing(RNA-seq),we sequenced the transcriptome of 24 matched tissue samples(primary tumor and paired adjacent normal tissues)from 12 Chinese HCC patients,and identified differentially expressed genes(DEGs)and differentially expressed IncRNAs(DELs).The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student's t-test or linear regression.Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis.Validation of DELs' functions including proliferation and migration was performed via loss-of-function RNAi assays.Results In this study,we identified 439 and 214 differentially expressed mRNAs(DEGs)and IncRNAs(DELs),respectively,in HCC.Furthermore,we validate these DEGs and DELs in 21 pairs of HCC tissue samples using quantitative real-time PCR(qRT-PCR).By analyzing the correlation between DELs and clinicopathological feathers,we found that the expression levels of multiple IncRNAs were significantly associated with tumor size,tumor histologic differentiation,portal vein tumor emboli(PVTT),the serum concentration and the tissue immunohistochemical(IHC)staining of a-fetoprotein(AFP).Specifically,the expression level of NONHSAT122051 was linearly correlated with the serum AFP concentration with,the p value of 0.0005,suggesting that NONHSAT122051 may serve as a novel biomarker candidate for HCC.In addition,we constructed the IncRNA-mRNA co-expression network,it was showed that DELs may correlated with metabolism,cell cycle,chemical carcinogenesis,and complement and coagulation cascade-related pathways.At last,we found that silencing the expression of NONHSAT122051 or NONHSAT003826 significantly attenuated the mobility of both SK-HEP-1 and SMMC-7721 HCC cells.Conclusion These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC by revealing the biological functions and possible molecular mechanisms of lncRNAs.