Background: The aberrant expression of circular RNAs (circRNAs) has been identified as a novel trait of cancers. However, the role of circRNAs in colorectal cancer (CRC) remains to be elucidated.
Methods: Informatic analysis was performed to identify circRNAs in CRC tissues and adjacent tissues. Gain- and loss-of-function experiments were constructed to analyze hsa_circ_001806 roles in CRC cell stemness by sphere-formation, ALDH activity, stemness marker expression and tumor-initiating ability assays. CCK8 cell viability was carried out to evaluate hsa_circ_0001806 roles in CRC cell viability. Luciferase reporter and pull-down assays were used to reveal the underlying mechanisms.
Results: Hsa_circ_0001806 was significantly upregulated in CRC tissues and correlated with TNM stage, depth of invasion, lymphatic metastasis and distant metastasis. Hsa_circ_0001806 promoted the stemness of CRC cells, as evident by increasing sphere-formation ability, ALDH1 activity and stemness marker expression while had no effect on cell viability. Mechanistically, the same miR-193-5p-binding sites are shared between hsa_circ_0001806 and COL1A1. Hsa_circ_0001806 upregulates COL1A1 expression in a miR-193-5p-dependent manner, which is essential for hsa_circ_0001806-mediated regulation on CRC cell stemness.
Conclusion: CircRNA hsa_circ_0001806 may act as a promising therapeutic target by facilitating the stemness of CRC cells via activating the hsa_circ_0001806/miR-193a-5p/COL1A1 axis.
Keywords: hsa_circ_0001806, miR-193a-5p, COL1A1, ceRNA, stemness, colorectal cancer