A Preliminary Study on the Pathogenesis of Colorectal Cancer by Constructing a Hsa-circRNA-0067835-miRNA-mRNA Regulatory Network

Abstract

Background: Increasing evidence shows that circular RNAs (circRNAs) play a key role in the development of colorectal cancer (CRC). An interesting candidate RNA in this context is hsa-circRNA-0067835 (circIFT80), but its network of actions is still unclear. Methods: Big data mining technology was used to explore the downstream microRNAs (miRNA) and messenger RNAs (mRNA) of the circIFT80 network. A regulatory network, comprising circIFT80 and its corresponding miRNAs and mRNAs, was derived to preliminarily explore the potential mechanism of circIFT80 in CRC. Finally, the proposed regulatory network was experimentally verified at the cellular level. Results: A total of 6 miRNAs were screened, of which hsa-miR-197-3p, hsa-miR-370-3p and hsa-miR-377-5p may be the most potential downstream miRNAs of hsa-circRNA -0067835 in CRC. A total of 74 up-regulated genes with opposite miRNA expression were selected for subsequent verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases revealed that the target genes occurred more frequently in cancer-related pathways. In addition, protein-protein interaction (PPI) analysis of the target genes revealed a set of involved genes from which the hubTop 10 genes were selected for further analysis. Moreover, circRNA-miRNA-hubTop 10 mRNA networks were constructed. According to this analysis, circIFT80 simultaneously regulates hsa-miR-197-3p, hsa-miR -370-3p, and hsa-miR-377-5p, among which hsa-miR-370-3p seems to be associated with further genes that may be relevant to CRC development. Therefore, the proposed circIFT80/ hsa-miR-370-3p/WNT7B, SLC1A5, RCBTB1 and COL6A6 signal axes were subjected to experimental verification. It could be shown that circIFT80 was up-regulated in CRC tissues. The circIFT80 was able to inhibit apoptosis and promote proliferation, migration and invasion. Moreover, circIFT80 inhibited the expression of hsa-miR-370-3p and promoted the expression of COL6A6, RCBTB1, SLC1A5 and WNT7B in CRC cell lines. Dual luciferase reporter assays further validated that circIFT80 is able to bind to hsa-miR-370-3p which in turn targets WNT7B. Conclusion:The circIFT80 may play a role in carcinogenesis through the new circIFT80/ hsa-miR-370-3p/WNT7B signal axis. These findings may provide potential biomarkers and therapeutic targets for the treatment of CRC.

The Network of miRNA–mRNA Interactions in Circulating T Cells of Patients Following Major Trauma – A Pilot Study

“… 40 Overexpression of hsa-miR-185-5p occurs in the vitreous of proliferative diabetic retinopathy patients, 41 in the pericardiac adipose tissue of patients with coronary artery disease, 42 and significantly enhances endothelial cell angiogenesis. 43 hsa-miR-197-3p is highly expressed in proliferative diabetic retinopathy patients, 44 , 45 is involved in the development of colorectal cancer 46 and non-small cell lung cancer, 47 and may act as a biomarker for follicular thyroid cancer. 48 Further, hsa-miR-485-5p is associated with lupus nephritis, 49 pulmonary tuberculosis, 50 and cancers such as lung cancer, 51 hepatocellular carcinoma, 52 oral tongue squamous cell carcinoma, 53 and glioblastoma.…”

Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer

“…Increasing evidence has supported that circRNAs participate in regulating tumorigenesis and drug resistance of CRC ( 100 , 101 ). Chen et al.…”

Recent advances in the diagnostic and therapeutic roles of microRNAs in colorectal cancer progression and metastasis

“…For example, lncRNA TUG1 can promote the growth and migration of CRC cells by secreting miR-145-5p, and the TUG1/miR-145-5p/TRPC6 pathway can serve as a target for CRC diagnosis and therapy (113). Liu et al showed that the circIFT80/hsa-miR-370-3p/WNT7B signalling axis might also play a role in carcinogenesis (114). CircIFT80 inhibits the expression of hsa-miR-370-3p in CRC cell lines, thereby inhibiting apoptosis.…”

“…Liu et al. showed that the circIFT80/hsa-miR-370-3p/WNT7B signalling axis might also play a role in carcinogenesis ( 114 ). CircIFT80 inhibits the expression of hsa-miR-370-3p in CRC cell lines, thereby inhibiting apoptosis.…”