Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) remains an extremely lethal disease worldwide. High-throughput methods have revealed global transcriptome dysregulation; however, a comprehensive investigation of the complexity and behavioral characteristics of the competing endogenous RNA (ceRNA) network in HCC is lacking. In this study, we extracted the transcriptome (RNA) sequencing data of 371 HCC patients from The Cancer Genome Atlas platform. With the comparison of the high Myc expression (Myc high ) tumor and low Myc expression (Myc low ) tumor groups in HCC, we identified 1,125 differentially expressed (DE) mRNAs, 589 long non-coding RNAs (lncRNAs), and 93 microRNAs (miRNAs). DE RNAs predicted the interactions necessary to construct an associated Myc ceRNA network, including 19 DE lncRNAs, 5 miRNAs, and 72 mRNAs. We identified a significant signature (long intergenic non-protein-coding [LINC] RNA 2691 [LINC02691] and LINC02499) that effectively predicted overall survival and had protective effects. The target genes of microRNA (miR)-212-3p predicted to intersect with DE mRNAs included SEC14-like protein 2 (SEC14L2) and solute carrier family 6 member 1 (SLC6A1), which were strongly correlated with survival and prognosis. With the use of the lncRNA-miRNA-mRNA axis, we constructed a ceRNA network containing four lncRNAs (LINC02691, LINC02499, LINC01354, and NAV2 antisense RNA 4), one miRNA (miR-212-3p), and two mRNAs (SEC14L2 and SLC6A1). Overall, we successfully constructed a mutually regulated ceRNA network and identified potential precision-targeted therapies and prognostic biomarkers.

Genomic Instability-Related LncRNA Signature Predicts the Prognosis and Highlights LINC01614 Is a Tumor Microenvironment-Related Oncogenic lncRNA of Papillary Thyroid Carcinoma

“…FOXD2-AS1 was recognized as a molecular biomarker and participated in chemo-resistance, malignant proliferation, invasion, and immunosuppression (46,(51)(52)(53)(54)(55). Recently, a study demonstrated that overexpression of FOXD2-AS1 was associated with poor clinical outcomes in PTC (57)(58)(59). GI-associated ceRNA regulatory network should be evaluated in the future studies.…”

Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs

“…Of the 81 IICDLs, 20 were significantly associated with prognosis of patients with HCC, namely, AL606489.1, AC004160.1, AC099508.2, TMEM220-AS1, AC079061.1, AC115619.1, LINC02754, LINC02037, AC008549.1, AP001065.3, LINC01018, LINC00261, LINC02362, AC009093.5, AC079466.1, LINC01554, AC010280.2, AP001781.1, LINC02499, and AL161645.2. Among them, AC079466.1 ( 65 ), LINC01554 ( 66 ), LINC00261 ( 67 – 69 ), LINC02499 ( 70 – 73 ), and AC008549.1 ( 74 ) were closely correlated with the prognosis of patients with HCC. In addition, patients with HCC had low levels of TMEM220-AS1, a protein that inhibits malignant behavior by increasing TMEM220 expression and inactivating Wnt/β-catenin ( 75 ).…”

Construction of a Novel MYC-Associated ceRNA Regulatory Network to Identify Prognostic Biomarkers in Colon Adenocarcinoma

“…ere is a growing number of pathophysiological roles for the MYC family in various cancers, including COAD [ [39][40][41]. We established a MYC-related ceRNA triple network in colon adenocarcinoma from the experience of our previous ceRNA network construction for liver cancer [42]. Firstly, by comparing the MYC high tumor tissues with Myc low tumor tissues, we identified 907 DElncRNAs, 337 DEmiRNAs, and 9204 DEmRNAs.…”