Background: Though circular RNAs, new non-coding RNA classes have demonstrated that they have an essential role in the initiation as well as development of CRC (colorectal cancer), whereas in CRC the function and mechanism of hsa_circ_0001666 are less known.
Methods: Hsa_circ_0001666 was identified by bioinformatics analysis of a circRNA microarray from the GEO database, and its expression in both CRC cell lines and tissues was analysed. A series of in vitro along with in vivo experiments were carried out for exploring the hsa_circ_0001666 functions, including transwell, wound healing, flow cytometry, colony formation, Edu, CCK-8, soft agar colony formation, tumor xenografts and lung/liver metastasis in mice. RNA pull-down, RIP (RNA immunoprecipitation), luciferase reporter assay, FISH (fluorescence in situ hybridization) and rescue experiments were used for determining the correlation among hsa_circ_0001666, miR-576-5p and PCDH10.
Results: Hsa_circ_0001666 was downregulated in both CRC cell lines along with tumour tissues. A higher expression level of hsa_circ_0001666 indicated a better clinical prognosis in patients with CRC. Hsa_circ_0001666 knockdown significantly supported CRC cell proliferation along with invasion and inhibited cell apoptosis in vitro. Hsa_circ_0001666 knockdown accelerated the CRC growth and metastasis in vivo. Moreover, the mechanistic study showed that hsa_circ_0001666, acting as 'ceRNA' of miR-576-5p, prevented PCDH10 downregulation, as well as suppressed EMT and stemness of CRC cells, and the Wnt/β-catenin signalling pathway. Inhibiting miR-576-5p or overexpressing PCDH10 could reverse phenotypic changes caused by knocking down of hsa_circ_0001666.
Conclusions: Hsa_circ_0001666 suppresses CRC progression through the miR-576-5p/PCDH10 axis and may provide a new insight for the diagnosis and treatment of CRC.
Keywords: PCDH10; ceRNA; colorectal cancer; hsa_circ_0001666; miR-576-5p.
© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.