| Background: Non-coding RNAs(ncRNAs)have been implicated in a range of developmental processes and diseases.However,there remain great challenges in fully illustrating the function and mechanism of non-coding RNAs(ncRNAs)underlying hepatocarcinogenesis.We aimed to characterize micro RNA(miRNA)and long non-coding RNA(lncRNA)in primary hepatocellular carcinoma(HCC)and constructed a multi-dimensional network among ncRNAs and mRNAs.Methods: We performed transcriptome sequencing(RNA-seq)in nine pathologically confirmed HCCs and their matched non-cancerous tissues.The expression profiles of miRNA and lncRNA were characterized,and a regulatory mRNA-lncRNA-miRNA(MLMI)network was constructed based on significantly differentially expressed(DE)ncRNAs and mRNAs.We have further over expressed the synthetical novel isoform of MEG3 in the Hep G2 and LO2 cell lines and then performed transcriptome sequencing analyses to validate the regulatory role of MEG3 in the MLMI networks among its targeted molecules.Results: Of the identified miRNA(n=203)and lncRNA(n=1,090),we noted 16 significantly DE miRNAs and three DE lncRNAs between HCCs and its matched cirrhosis tissues.We detected potential pairwise interactions between DE ncRNAs and mRNAs in the same cohort,including extensive interactions uncharacterized previously.These DE RNAs were highly enriched in functional pathways implicated in HCC(n=21,p-adjusted<0.05),e.g.,P53,MAPK,and NAFLD signaling.We constructed an MLMI network of reciprocal interactions of 16 miRNAs,three lncRNAs,and 249 mRNAs in HCC.The overexpression of MEG3 validated its predominant role in the MLMI network in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs were changed significantly.Conclusion: Our results suggested that a comprehensive MLMI network may function in modulating carcinogenesis.The crosstalk of the network provides a new avenue for accurately understanding the molecular mechanisms of hepatocarcinogenesis. |
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