Abstract
Circular RNA (circRNA), a type of RNA that is widely expressed in mammalian cells, is considered to be essential in tumorigenesis. CircRNA can regulate target gene expression by interacting with the corresponding microRNA (miRNA). Our preliminary results showed that the expression levels of 1,817 circRNAs were significantly different in colon cancer tissue compared with paracancerous tissue, of which 1,236 were upregulated and 581 were downregulated. By using RT-PCR, we confirmed that the expression of hsa_circ_0007843, hsa_circ_0010575, hsa_circ_0007331, and hsa_circ_0001615 was significantly higher in colon cancer tissue than in normal colonic tissue; however, the expression levels of hsa_circ_0014879 and hsa_circRNA_401801 were not significantly different between normal and neoplastic colonic tissue. Among the circRNAs that were confirmed to be upregulated in colon cancer tissue, hsa_circ_0007843 was also found to be highly expressed in colon cancer SW480 cells. Overexpression of hsa_circ_0007843 promoted the invasion and migration of SW480 cells, whereas its downregulation suppressed their invasion and migration. Overexpression of hsa_circ_0007843 promoted tumor growth, whereas its downregulation inhibited tumor growth. We found that hsa_circ_0007843 interacted with miR-518c-5p and suppressed its expression, and miR-518c-5p interacted with matrix metallopeptidase 2 (MMP2) and promoted its expression and translation. Taken together, this study demonstrated that hsa_circ_0007843 acted as an miRNA sponge to regulate MMP2 expression by removing the inhibitory effect of miR-518c-5p on MMP2 gene translation, which further affected the invasive capability of SW480 cells.
Highlights
Colon cancer, a common gastrointestinal tumor, remains a serious threat to human health with the 3rd highest morbidity and mortality rate worldwide (Siegel et al, 2017)
Total RNA was isolated from 4 colon cancer tissue samples and 4 paracancerous tissue samples that were separated by a margin of 5 cm
By using Circular RNA (circRNA) microarray and reverse transcription polymerase chain reaction (RT-PCR) analyses, we identified four circRNAs that were significantly upregulated in colon cancer tissue
Summary
A common gastrointestinal tumor, remains a serious threat to human health with the 3rd highest morbidity and mortality rate worldwide (Siegel et al, 2017). The development of colon cancer is a multistep process in which the abnormal expression of genes plays an important role (Qi and Ding, 2018). Colon cancer has been studied widely, its pathogenesis is not fully understood. In-depth studies are required for the further elucidation of the molecular mechanism involved in the carcinogenesis of human colon cancer, which will provide new insights for the diagnosis, prognosis, and treatment of colon cancer. CircRNAs are largely expressed in the eukaryotic transcriptome and participate in the regulation of gene expression (Guttman and Rinn, 2012; Holdt et al, 2018) and can be considered essential in tumorigenesis (Arnaiz et al, 2018)
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