Identification of circRNA Biomarker for Gastric Cancer through Integrated Analysis

Abstract

Gastric cancer (GC) is one of the most common malignant tumors and ranks third in cancer mortality globally. Although, a lot of advancements have been made in diagnosis and treatment of gastric cancer, there is still lack of ideal biomarker for the diagnosis and treatment of gastric cancer. Due to the poor prognosis, the survival rate is not improved much. Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure that don’t have the 5′-3′ polarity and a 3′ polyA tail. Because of their circular structure, circRNAs are more stable than linear RNAs. Previous studies have found that circRNAs are involved in several biological processes like cell cycle, proliferation, apoptosis, autophagy, migration and invasion in different cancers, and participate in some molecular mechanisms including sponging microRNAs (miRNAs), protein translation and binding to RNA-binding proteins. Several studies have reported that circRNAs play crucial role in the occurrence and development of different types of cancers. Although, some studies have reported several circRNAs in gastric cancer, more studies are needed in searching new biomarkers for gastric cancer diagnosis and treatment. Here, we investigated potential circRNA biomarkers for GC using next-generation sequencing (NGS) data collected from 5 paired GC samples. A total of 45,783 circRNAs were identified in all samples and among them 478 were differentially expressed (DE). The gene ontology (GO) analysis of the host genes of the DE circRNAs showed that some genes were enriched in several important biological processes, molecular functions and cellular components. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that some host genes were enriched in several GC related pathways. The circRNA-miRNA-gene interaction network analysis showed that two circRNAs circCEACAM5 and circCOL1A1 were interacted with gastric cancer related miRNAs, and their host genes were also the important therapeutic and prognostic biomarkers for GC. The experimental results also validated that these two circRNAs were DE in GC compared to adjacent normal tissues. Overall, our findings suggest that these two circRNAs circCEACAM5 and circCOL1A1 might be the potential biomarkers for the diagnosis and treatment of GC.

Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer

“…To investigate potential dysregulated circRNAs in GC, high-throughput circRNA sequencing with ribosomal RNA depletion was conducted using five paired GC and non-tumoral tissues [ 24 , 37 ]. A total of 478 dysregulated circRNAs (fold change ≥2, P < 0.05) were identified, suggesting that these circRNAs may participate in GC development (Fig.…”

CircRNA_0044556 regulates paclitaxel resistance in triple-negative breast cancer by targeting miR-665

“…PTX increased circRNA_0044556 expression in MDA-MB-231 cells, suggesting that circRNA_0044556 may be related to paclitaxel resistance. As a circRNA encoded by COL1A1, previous studies have shown that circRNA_0044556 plays a vital role in the occurrence and development of tumors, including colorectal cancer [20,21], gastric cancer [22] and TNBC [12]. The in nite malignant proliferation of tumor cells and inhibition of apoptosis are the core factors in tumor development and change [23,24].…”

Circular RNAs Variously Participate in Coronary Atherogenesis

“…Indeed, one circRNA can adsorb several miRNAs, one miRNA molecule can target a wide range of different mRNAs with the involvement of corresponding protein products in the development of several pathologies, and individual circRNAs can be markers of several diseases simultaneously. Many circRNAs, in particular circMTO1, circHIPK3, сirc_0001946, circPTPRA, and circCOL1A1, are potential targets for therapy or biomarkers of CAD ( Table 1 and Table 2 ), and play critical roles in cancer progression as well [ 175 , 176 , 177 , 178 , 179 ]. Additional comprehensive studies of the action mechanisms of individual circRNAs and the involved regulatory networks are needed.…”