Hsa_circ_0001658 Accelerates the Progression of Colorectal Cancer Through MiR-590-5p/METTL3 Regulatory Axis

Background: As reported, multiple circular RNAs (circRNAs) interfere with colorectal cancer (CRC) progression. Here, circRNA_0001658 (circ_0001658) is focused on studying how it works in CRC.

Aim: Clarify the expression pattern, biological function, and underlying mechanism of circ_0001658 of CRC tumorigenesis.

Methods: In CRC-related chip data retrieved using the database named Gene Expression Omnibus, different expressions of circRNAs between CRC and normal tissue samples were identified. Quantitative Real-time PCR and Western blot ensured the analysis on circ_0001658, microRNA-590-5P (miR-590-5p), and methyltransferase-like 3 (METTL3) mRNA expressions in tissues and cells. Cell counting kit-8 and flow cytometry were used to detect cell proliferation, apoptosis and migration. The targeting relations between circ_0001658, miR-590-5p, and METTL3 mRNA 3'-untranslated region were under the verification of bioinformatics prediction and dual luciferase-based reporter gene assays. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were employed on the downstream targets of miR-590-5p using the Database for Annotation, Visualization and Integrated Discovery database.

Results: Circ_0001658 and METTL3 mRNA was elevated in CRC tissues and cells, whereas miR-590-5p was decreased. Circ_0001658 overexpression promoted the proliferation of HT29 cells, inhibited apoptosis, and accelerated the cell cycle. In SW480 cells, knocking down circ_0001658 had the opposite effect. Circ_0001658 could specifically bind to miR-590-5p and negatively modulate its expressions; METTL3 is a miR-590-5p target that can be positively regulated by circ 0001658. Circ 0001658 was inversely associated with miR-590-5p expression while positively with METTL3 expressions.

Conclusion: Circ_0001658 regulates the miR-590-5p/METTL 3-axis to increase CRC cell growth and decrease apoptosis.