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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 (Mychigh) tumor and low Myc expression (Myclow) 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.
Highlights
We divided the transcriptome data of 371 Hepatocellular carcinoma (HCC) tissues into Mychigh tumor and Myclow tumor groups based on the standard median expression of Myc
Clinical analysis of Myc overexpression in HCC To explore whether Myc affects gene expression in liver cancer, we divided liver cancer patients into Mychigh tumor and Myclow tumor groups based on the median values of Myc in this study
Studies have been conducted to construct a competing endogenous RNA (ceRNA) network between HCC tissues and adjacent nontumor liver tissues.[60]
Summary
Liver cancer is categorized as primary hepatic cancer and metastatic hepatic cancer.[1,2,3] Hepatocellular carcinoma (HCC) is the fifthmost common cancer worldwide and is a highly lethal malignancy, accounting for nearly 80% of all primary liver malignancies.[4,5,6] According to 2018 Global Cancer statistics,[7] there have been more than 100,000 new cases and deaths worldwide every year. there have been great advancements in cancer therapy, the 5-year overall survival (OS) rate for HCC is still only 12.10%.8–11 Surgical resection, liver transplantation, and chemotherapy are common therapies,[12,13,14,15] but they are appropriate only for patients with earlystage disease.[16,17] it is essential to understand the mechanisms underlying the pathogenesis of HCC and identify novel biomarkers. Liver cancer is categorized as primary hepatic cancer and metastatic hepatic cancer.[1,2,3] Hepatocellular carcinoma (HCC) is the fifthmost common cancer worldwide and is a highly lethal malignancy, accounting for nearly 80% of all primary liver malignancies.[4,5,6] According to 2018 Global Cancer statistics,[7] there have been more than 100,000 new cases and deaths worldwide every year. There have been great advancements in cancer therapy, the 5-year overall survival (OS) rate for HCC is still only 12.10%.8–11. Liver transplantation, and chemotherapy are common therapies,[12,13,14,15] but they are appropriate only for patients with earlystage disease.[16,17] it is essential to understand the mechanisms underlying the pathogenesis of HCC and identify novel biomarkers
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