The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?

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.

The circular RNA circ0005654 interacts with specificity protein 1 via microRNA-363 sequestration to promote gastric cancer progression

“…Gene functional enrichment conducted by Pereira et al . indicated that circRNA/miRNA/mRNA axes have the potency to directly affect pathways that are well-known to be dysregulated in the event of gastric carcinogenesis [ 22 ]. Our results demonstrated that circ0005654 was mainly concentrated in the cytoplasm, and dual-luciferase reporter assay was performed to confirm that circ0005654 could competitively share miR-363 with sp1 mRNA, serving as a sponge.…”

Knockdown of circ-FURIN suppresses the proliferation and induces apoptosis of granular cells in polycystic ovary syndrome via miR-195-5p/BCL2 axis

“…It is well known that circRNAs perform multiple functions via sponging miRNAs and RNA-binding proteins [ 26 ]. Our study found that miR-195-5p could directly bind with circ-FURIN, and BCL2, suggesting that circ-FURIN or BCL2 have targeted relationship with miR-195-5p.…”

The Molecular Roles and Clinical Implications of Non-Coding RNAs in Gastric Cancer

“…Hif-2α is upregulated in hypoxic drug-resistant GC (HRGC) cells under a long-term hypoxic microenvironment and promotes GC metastasis through the miR-653-5p/miR-338-3P-NRP1 axis ( Jin et al, 2020b ). These circRNAs, which form complex RBP-circRNA-miRNA-mRNA interaction networks, such as the circHIPK3/miR-29b-c/COL1A2 network, are involved in GC development, progression, and reduced sensitivity to chemotherapy ( Pereira et al, 2020 ).…”