Abstract
Circular RNAs (circRNAs) are a new class of long noncoding RNAs able to perform multiple functions, including sponging microRNAs (miRNAs) and RNA-Binding Proteins (RBPs). They play an important role in gastric carcinogenesis, but its involvement during gastric cancer (GC) development and progression are not well understood. We gathered miRNA and/or RBPs sponge circRNAs present in GC, and accessed their biological roles through functional enrichment of their target genes or ligand RBPs. We identified 54 sponge circRNAs in GC that are able to sponge 51 miRNAs and 103 RBPs. Then, we evaluated their host gene expression using The Cancer Genome Atlas (TCGA) database and observed that COL1A2 is the most overexpressed gene, which may be due to circHIPK3/miR-29b-c/COL1A2 axis dysregulation. We identified 27 GC-related pathways that may be affected mainly by circPVT1, circHIPK3 and circNF1. Our results indicate that circHIPK3/miR-107/BDNF/LIN28 axis may mediate chemoresistance in GC, and that circPVT1, circHIPK3, circNF1, ciRS-7 and circ_0000096 appear to be involved in gastrointestinal cancer development. Lastly, circHIPK3, circNRIP1 and circSMARCA5 were identified in different ethnic populations and may be ubiquitous modulators of gastric carcinogenesis. Overall, the studied sponge circRNAs are part of a complex RBP-circRNA-miRNA-mRNA interaction network, and are involved in the establishment, chemoresistance and progression of GC.
Highlights
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cancer-related deaths worldwide [1]
Our results indicate that the sponge circRNAs in GC are part of a complex RNA-Binding Proteins (RBPs)-circRNA-miRNA-mRNA
Through the mRNA-miRNA-circRNA interaction, we identified 23 sponge circRNAs that can regulate these miRNAs and may affect the expression of their target genes directly involved in the gastric cancer pathway
Summary
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cancer-related deaths worldwide [1]. It is an aggressive disease, whose five-year survival rate is high in some countries like Japan (60%) and South Korea (69%); in regions such as South and. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) [5] and circular. RNAs (circRNAs) [6], are dysregulated during this disease onset and progression. CircRNAs are a new class of long noncoding RNAs that have their 50 and 30 ends covalently joined [7,8]. Current knowledge of circRNAs suggests that they can perform multiple functions, Cancers 2020, 12, 1982; doi:10.3390/cancers12071982 www.mdpi.com/journal/cancers
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