Computational identifying and characterizing circular RNAs and their associated genes in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is currently still a major factor leading to death, lacking of reliable biomarkers. Therefore, deep understanding the pathogenesis for HCC is of great importance. The emergence of circular RNA (circRNA) provides a new way to study the pathogenesis of human disease. Here, we employed the prediction tool to identify circRNAs based on RNA-seq data. Then, to investigate the biological function of the circRNA, the candidate circRNAs were associated with the protein-coding genes (PCGs) by GREAT. We found significant candidate circRNAs expression alterations between normal and tumor samples. Additionally, the PCGs associated with these candidate circRNAs were also found have discriminative expression patterns between normal and tumor samples. The enrichment analysis illustrated that these PCGs were predominantly enriched for liver/cardiovascular-related diseases such as atherosclerosis, myocardial ischemia and coronary heart disease, and participated in various metabolic processes. Together, a further network analysis indicated that these PCGs play important roles in the regulatory and the PPI network. Finally, we built a classification model to distinguish normal and tumor samples by using candidate circRNAs and their associated genes, respectively. Both of them obtained satisfactory results (~ 0.99 of AUC for circRNA and PCG). Our findings suggested that the circRNA could be a critical factor in HCC, providing a useful resource to explore the pathogenesis of HCC.

Polymorphisms and expression pattern of circular RNA circ-ITCH contributes to the carcinogenesis of hepatocellular carcinoma

“…They could be used as molecular markers or potential targets for early tumor diagnosis, therapeutic evaluation, prognosis prediction, and even gene therapy for tumors [ 15 ]. Li et al [ 26 ] found circRNA could be a critical factor in HCC using RNA-seq data of 100 samples consisting of tumor tissues and para-carcinoma tissues from 50 HCC patients were downloaded from the Sequence Reads Archive (SRP068976). Recent studies demonstrated that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway [ 24 , 25 , 27 ].…”

Screening of up‑ and downregulation of circRNAs in HBV‑related hepatocellular carcinoma by microarray

“…Abnormal circRNAs have been identified to be involved in the occurrence and development of HCC (51). In a previous study, the RNA-seq data from 50 paired HCC tissues and NTs were analyzed to identify the function of circRNAs in HCC (51).…”

“…Abnormal circRNAs have been identified to be involved in the occurrence and development of HCC (51). In a previous study, the RNA-seq data from 50 paired HCC tissues and NTs were analyzed to identify the function of circRNAs in HCC (51). Protein-coding genes (PCGs) associated with the 2091 circRNAs were identified to be enriched predominantly on liver/cardiovascular-related diseases, and participated in a number of metabolic processes (51).…”

“…In a previous study, the RNA-seq data from 50 paired HCC tissues and NTs were analyzed to identify the function of circRNAs in HCC (51). Protein-coding genes (PCGs) associated with the 2091 circRNAs were identified to be enriched predominantly on liver/cardiovascular-related diseases, and participated in a number of metabolic processes (51). A total of 45 circRNAs and 23 PCGs exhibited significant expression alterations between HCC and normal tissues (51).…”

Screening circular RNA expression patterns following focal cerebral ischemia in mice

“…In addition, circRNAs also regulate their parental gene expressions. Accumulating evidence has demonstrated that circRNAs are involved in tissue and disease developments, including neuronal development, Alzheimer’s Disease, cardiovascular diseases, and cancers [ 7 – 13 ]. However, the research articles regarding to circRNA in stroke have not been reported.…”