Abstract
BackgroundEmerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained.MethodsThe expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments.ResultsThe expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis.ConclusionsZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.
Highlights
Emerging evidence has shown that dysregulated expression of long noncoding RNAs is implicated in liver hepatocellular carcinoma (HCC)
When the 807 differentially upregulated The Cancer Genome Atlas (TCGA) long noncoding RNAs (lncRNAs) were cross-referenced with 398 lncRNAs upregulated in the experimental sample, a total of 8 overlapping lncRNAs were identified, as shown in Fig. 1c Between the 72 differentially downregulated TCGA lncRNAs and the 1037 lncRNAs that were downregulated in the experimental samples there were 6 overlapping lncRNAs, as shown in Fig. 1d, which totaled 14 overlapping genes
LncRNA ZFPM2-AS1 acts AS a competing endogenous RNA (ceRNA) in the regulation of GDF10 expression by binding to miR-139 To identify the potential miRNA targets of lncRNAZFPM2AS1, in silico analysis was performed by using the Microcode database, and the results showed that multiple miRNAs may act as biological targets of lncRNA ZFPM2-AS1
Summary
Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). Liver transplantation and tumor ablation are potentially curative therapies [3,4,5]; these treatment options are only applicable to patients with early stage disease [6, 7]. High-throughput genome and transcriptome sequencing and microarrays have indicated that apart from protein-coding genes, 75% of the human genomeis transcribed into noncoding RNAs [8]. LncRNAs are functionally catalogued as noncoding transcripts, are more than 200 nucleotides in length, and have no protein-coding potential. Mounting evidence has indicated that lncRNAs are implicated in a variety of biological processes, including chromatin interaction, transcriptional regulation, mRNA posttranscriptional regulation and epigenetic regulation [11,12,13]
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