Most patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, are first identified at advanced stages precluding surgical removal of the affected tissue. Due to the lack of obvious clinical symptoms at the early stages of the disease, in-depth understanding of the biological and molecular complexities of the disease process, and effective biomarkers in HCC, survival upon diagnosis remains short.

“HCC, as the most common type of liver cancer, has become one of the main causes of cancer-related death, and it is also a global health problem that has attracted widespread attention,” say Huifang Liang, PhD, and Bixiang Zhang, PhD, from The Huazhong University of Science and Technology and The Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases.

Several recent studies have found mechanisms that regulate the competing endogenous RNA (ceRNA) network affect the incidence and development of HCC. The ceRNA network is a complex post-transcriptional regulatory network where circular RNAs (circRNAs), long noncoding RNAs (lncRNAs) and protein-coding mRNAs compete with microRNAs (miRNAs) through at least one shared miRNA response element (MRE).

A new study led by scientists at Tongji Medical College, in Hubei China, investigates the ceRNA network to better understand the complex gene interactions in HCC and identify potential biomarkers to diagnose and treat HCC.

Their findings are published in the article “Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma” in the journal Aging-US, and may help better understand ceRNA mechanisms driving HCC, and provide new biomarkers to evaluate the prognosis of HCC.

The researchers compare RNA sequencing data available in public TCGA and GEO databases to identify mRNAs, lncRNAs and circRNAs that are expressed at different levels in HCC and normal tissues and predict target miRNAs of differentially expressed (DE) circRNAs and lncRNAs to construct a prognostic circRNA-lncRNA-miRNA-mRNA ceRNA network for HCC. They establish a seven-gene HCC signature and validate one hub gene in the prognostic signature, DTYMK, as a new potential biomarker.

Scientists construct a prognostic competitive endogenous RNA network to identify complex gene interactions in hepatocellular carcinoma (Huifang Liang and Bixiang Zhang)

Based on the targeting relationships between 7 hub mRNAs and other RNAs, the researchers establish the prognostic ceRNA network of 21 circRNAs, 15 lncRNAs, 5 miRNAs, and 7 mRNAs.

The authors point out that the limitation of the current study is that performing in vivo and in vitro experiments to verify the function of DTYMK in HCC was beyond the scope of the study and needs to be done in future studies. They also suggest verifying the role of other hub ncRNAs in the prognostic ceRNA network in future experiments.