Abstract
BACKGROUND: Among all malignancies, colorectal cancer ranks third in incidence rate and second in mortality rate. Human beta-defensin-1 (hBD-1) has broad-spectrum antimicrobial properties, and it plays an important role in the tumor microenvironment. Circular ribonucleic acids (circRNAs) regulate the proliferation and progression of colorectal cancer cells via cancer-related signaling pathways. METHODS: Cell proliferation was assessed using the Cell Counting Kit-8 assay to determine the optimal hBD-1 concentration. Intracellular autophagic vesicles were visualized via monodansylcadaverine staining. In addition, the levels of AKT and mammalian target of rapamycin (mTOR)-associated signaling proteins were analyzed via Western blot analysis. CircRNA microarrays and quantitative real-time polymerase chain reaction were used to identify differentially expressed circRNAs in colon cancer cell lines. The functional role of HAS-CIRCpedia-5280 in vitro was demonstrated by overexpressing HAS-CIRCpedia-5280 and inhibiting miR-4712-5p. HAS-CIRCpedia-5280 could be a sponge of miR-4712-5p, mimicking the effect induced by HAS-CIRCpedia-5280 overexpression in colon cancer cells. RESULTS: hBD-1 inhibited the proliferation of colon cancer cells and increased the number of intracellular autophagic vesicles. In addition, hBD-1 inhibited the AKT/mTOR signaling pathway, thereby enhancing cellular autophagy. Further, the interaction of HAS-CIRCpedia-5280 and miR-4712-5p was investigated. hBD-1 upregulated the expression level of HAS-CIRCpedia-5280 and downregulated the expression level of miR-4712-5p in colon cancer cells. Subsequently, the overexpression of HAS-CIRCpedia-5280 or the inhibition of miR-4712-5p activated the AKT/mTOR signaling pathway, leading to cellular autophagy inhibition. Conversely, the mimicry of miR-4712-p counteracted the effect of HAS-CIRCpedia 5280 overexpression in colon cancer cells by inhibiting the activation of the AKT/mTOR signaling pathway and, thereby, enhancing cellular autophagy. CONCLUSION: hBD-1 can have an inhibitory effect against cell proliferation in colon cancer SW-620/HCT-116 cells via the HAS-CIRCpedia-5280/miR-4712-5p-mediated activation of autophagy.