Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis and a high incidence. The molecular changes and novel biomarkers of HCC need to be identified to improve the diagnosis and prognosis of this disease. We investigated the current research concentrations of HCC and identified the transcriptomics-related biomarkers of HCC from The Cancer Genome Atlas (TGCA) database. Methods We investigated the current research concentrations of HCC using literature metrology analysis for studies conducted from 2008 to 2018. We identified long noncoding RNAs (lncRNAs) that correlated with the clinical features and survival prognoses of HCC from The Cancer Genome Atlas (TGCA) database. Differentially expressed genes (lncRNAs, miRNAs, and mRNAs) were also identified by TCGA datasets in HCC tumor tissues. A lncRNA competitive endogenous RNA (ceRNA) network was constructed from lncRNAs based on intersected lncRNAs. Survival times and the association between the expression levels of the key lncRNAs of the ceRNA network and the clinicopathological characteristics of HCC patients were analyzed using TCGA. Real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the results in tissue samples from 20 newly-diagnosed HCC patients. Results Analysis of the literature pertaining to HCC research revealed that current research is focused on lncRNA functions in tumorigenesis and tumor development. A total of 128 HCC dysregulated lncRNAs were identified; 66 were included in the co-expressed ceRNA network. We analyzed survival times and the associations between the expression of 66 key lncRNAs and the clinicopathological features of the HCC patients identified from TCGA. Twenty-six lncRNAs were associated with clinical features of HCC (P < 0.05) and six key lncRNAs were associated with survival time (log-rank test P < 0.05). Six key lncRNAs were selected for the validation of their expression levels in 20 patients with newly diagnosed HCC using qRT-PCR. Consistent fold changes in the trends of up and down regulation between qRT-PCR validation and TCGA proved the reliability of our bioinformatics analysis. Conclusions We used integrative bioinformatics analysis of the TCGA datasets to improve our understanding of the regulatory mechanisms involved with the functional features of lncRNAs in HCC. The results revealed that lncRNAs are potential diagnostic and prognostic biomarkers of HCC.

Screening a novel signature and predicting the immune landscape of metastatic osteosarcoma in children via immune-related lncRNAs

“…Based on knowledge that coding RNA and non-coding RNA play essential roles in malignancies, studies are now using them to predict the prognosis of multiple cancer types, such as gastric cancer, hepatocellular carcinoma, and bladder cancer (16)(17)(18). Most of these studies' signatures were analyzed by quantifying the transcriptional expression levels.…”

De Novo Profiling of Long Non-Coding RNAs Involved in MC-LR-Induced Liver Injury in Whitefish: Discovery and Perspectives

“…Similarly, we also observed enriched transcripts involved in the metabolic pathways, for example, GTP cyclohydrolase 1 encoded by the GCH1 gene, which is responsible for the hydrolysis of guanosine triphosphate (GTP). In a recent study, GCH1 was found enriched in human hepatocellular carcinoma [ 57 ]. GCH1 gene expression is regulated post-translationally, e.g., by phosphorylation [ 58 ], but it was also shown that GCH1 mRNA is a target of miR-133a in endothelial cells [ 59 ].…”

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

“…Exosomal lncRNA-miRNA-mRNA axes. lncRNAs are involved in the regulation of cell functioning due to their interaction with miRNAs to sponge them from their target mRNA; therefore, they can act as competitive endogenous RNAs (ceRNAs) (110). For example, lncRNA H19 promotes proliferation and migration but inhibits apoptosis of HCC cells via sponging miR-520a-3p, thereby, upregulating the LIMK1 gene that encodes the LIM domain kinase 1 protein (111).…”