Genome-Wide Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Hepatocellular Carcinoma

Abstract

Background/Aims: 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). Methods: 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. Results: 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. Conclusion: 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.

Inhibition of microRNA‐124a attenuates non‐alcoholic fatty liver disease through upregulation of adipose triglyceride lipase and the effect of liraglutide intervention

“…a). To identify miRNAs potentially binding the 3′‐UTR of ATGL mRNA, bioinformatic systems, including TargetScan, PicTar, and miRanda programs, were applied . Some miRNAs, such as miR‐124a, miR‐148a, miR‐148b, miR‐152, and miR‐485, tend to directly bind to the 3′‐UTR of ATGL mRNA.…”

The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma

“…Several studies have explored the prognostic biomarkers and possible molecular regulatory pathways of HCC based on competitive endogenous regulatory networks, but did not construct corresponding prognostic models for OS of HCC patients . One mRNA‐based prognostic model was built for OS of HCC patients through a single dataset from TCGA, but did not carry out external validation . Additionally, the calculation formula of this previous prognostic model was too complex for clinical utility and the results were difficult to interpret.…”

“…Long noncoding RNAs could indirectly regulate the expression of mRNAs through competitively binding response elements of miRNAs as endogenous molecular sponges . Several studies have explored the molecular biological regulatory mechanisms for prognosis of HCC patients through the ceRNA regulatory network . Lin et al constructed 3 prognostic prediction models by using lncRNAs, miRNAs, and mRNAs, whereas Bai et al constructed an lncRNA prognostic model for OS in HCC patients based on 13 lncRNAs identified by a ceRNA regulatory network.…”

“…Several studies have explored the molecular biological regulatory mechanisms for prognosis of HCC patients through the ceRNA regulatory network . Lin et al constructed 3 prognostic prediction models by using lncRNAs, miRNAs, and mRNAs, whereas Bai et al constructed an lncRNA prognostic model for OS in HCC patients based on 13 lncRNAs identified by a ceRNA regulatory network. However, these prognostic models were limited by the following reasons: complex calculation formulas, results with unclear prognostic significance, and lack of external validation.…”

Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

“…However, regulation of the reproductive system is complicated. Recently, the mechanism of competing endogenous RNAs (ceRNA) was reported as a speci c regulatory pathway of lncRNA, miRNA, and mRNA to explain how they exert their in uence on protein levels [29][30][31]. LncRNAs, as competing endogenous ceRNAs, can indirectly regulate mRNAs by acting as miRNA sponges.…”