Abstract
Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. However, the role of circRNAs still remains unknown in gastrointestinal stromal tumors (GISTs). In the present study, the differential circRNA expression profile of GISTs was screened by human circRNAs chip and verified by qRT-PCR. The circRNA–miRNA–mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore circRNA functions. Six significantly differential circRNAs were also verified in 20 pairs of GISTs and adjacent tissues by qRT-PCR. The result showed that a total of 543 differentially expressed circRNAs were identified in GISTs, of which 242 were up-regulated and 301 were down-regulated. Additionally, the circRNA–miRNA–mRNA network contained six circRNAs, 30 miRNAs, and 308 mRNAs, and the targeted mRNAs were associated with “regulation of biological process,” “intracellular organelle,” “protein binding,” and enriched in Wnt signaling pathway. Furthermore, qRT-PCR demonstrated that hsa_circRNA_061346, hsa_circRNA_103114, and hsa_circRNA_103870 were significantly up-regulated in GISTs (n = 20), and hsa_ circRNA_405324, hsa_circRNA_406821, and hsa_circRNA_000361 were dramatically down-regulated in GISTs (n = 20). In addition, all of these circRNAs were shown to have high diagnostic values, and most of them were significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs (P < 0.05). Therefore, we concluded that circRNAs were abnormally expressed in GISTs, and the circRNA–miRNA–mRNA regulatory network plays an important role in the occurrence and development of GISTs. Also, the identified six candidate circRNAs might be critical circRNAs and may present as potential diagnostic biomarkers for GISTs.
Highlights
Gastrointestinal stromal tumors are rarely one of the gastrointestinal carcinomas that originate from mesenchymal tissue
Circular RNA is a novel class of endogenous non-coding RNA characterized with 3 - and 5 -ends covalently linked in a closed-loop structure (Mahmoudi et al, 2020), which makes circRNAs resistant to exonucleases and more stable than traditional linear RNA, such as lncRNA and miRNA (Ding et al, 2020)
The circRNAs can be divided into four types according to the source (Meng et al, 2017): exonic circRNAs, intronic circRNA, exonic– intronic circRNA (EIciRNA), and intergenic circRNAs
Summary
Gastrointestinal stromal tumors are rarely one of the gastrointestinal carcinomas that originate from mesenchymal tissue. A few effective tumor biomarkers are used for GIST diagnosis and prediction (Etherington and DeMatteo, 2019). CircRNAs may act as microRNA (miRNA/miR) sponges by competitively binding to miRNA response elements to influence downstream target gene expression, as well as affecting gene function at a post-translational level, and the same circRNA can regulate multiple miRNAs. the same miRNAs can regulate multiple mRNA genes, thereby forming a large circRNA– miRNA–mRNA competitive network to affect the development of tumors (Xu S. et al, 2018). Recent studies (Lu et al, 2018; Chaichian et al, 2020) have demonstrated that circRNA abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. CircRNAs are of great importance as a biomarker for cancer diagnosis, cancer prediction, and treatment feedback, and may even serve as targets for cancer treatment
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