Genome-Wide Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Hepatocellular Carcinoma.Cell Physiol Biochem. 2018; 48(5):1953-1967.CP
Hepatocellular carcinoma (HCC) is the most prevalent subtype of primary liver tumor worldwide. Growing evidence has led to a consensus that long non-coding RNAs (lncRNAs) have considerable influence on tumorigenesis and tumor progression of HCC via the mechanism of competing endogenous RNAs (ceRNAs).
Here, we systematically investigated the expression landscape and clinical prognostic value of lncRNAs, micorRNAs (miRNAs), and mRNAs from The Cancer Genome Atlas. Differentially expressed RNAs were submitted to Cox regression analysis and the construction of prognostic indexes. A lncRNA-miRNA-mRNA regulatory network was then constructed based on interaction information derived from miRcode, TargetScan, miRTarBase, and miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to reveal and determine the functional roles of the ceRNA network in the prognosis of HCC.
We detected 77 differentially expressed lncRNAs, 29 differentially expressed miRNAs, and 1014 differentially expressed mRNAs in HCC, which were significantly associated with the overall survival of patients with HCC. We developed three prognostic prediction models that showed moderate predicting prognosis performance and were highly correlated with tumor burden, histological grade and pathological stage. Additionally, 10 survival-related lncRNAs, 6 survival-related miRNAs, and 31 survival-related mRNAs were included to develop a ceRNA network. Further functional enrichment analysis suggested that the ceRNA network was associated with a dismal prognosis for patients with HCC by disturbing the homeostasis of the cell cycle.
Together, our study highlights the significant roles of lncRNAs in the development and implementation of monitoring surveillance and prognosis of HCC and provides a deeper understanding of the lncRNA-related ceRNA regulatory mechanism in the pathogenesis of HCC.