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 sphereformation 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.
Tight junction proteins play crucial roles in maintaining the integrity of intestinal mucosal barrier. MiRNA-182-5p is capable of targeting claudin-2 which is one of the vital tight junction proteins and the effect and mechanism of miRNA-182-5p was explored here in the DSS-induced colitis model. The pathological conditions were evaluated via hematoxylin and eosin staining. The gene expression level was assessed via PCR. Quantitative immunohistochemistry analysis was performed for the measurement of claudin-2. microRNA.org online tool was used for target gene prediction. Luciferase reporter assay and RNA pull-down assay were performed to detect the target of miRNA-182-5p. The inflammatory and oxidative stress level were measured using corresponding kits. MiRNA-182-5p was highly expressed in colitis model and miRNA-182-5p inhibitor exerted protective effects on colitis induced by DSS in mice. The protective effects includded improvement of pathological changes, increases in anti-inflammation and anti-oxidative genes, and up-regulation of TGF-β1. Claudin-2 mRNA was predicted as the target of miRNA-182-5p, which was validated via luciferase reporter assay and RNA pull-down assay. Claudin-2 overexpression was found in miRNA-182-5p inhibitor group. Consistent with the role of miRNA-182-5p, claudin-2 overexpression also exerted protective effects on DSS-induced colitis in mice. Inhibition of miRNA-182-5p exerted protective effects on colitis via targeting and upregulating claudin-2. The findings in study provide a new therapeutic strategy for colitis treatment and lay the foundation for future study.
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