miR-338-5p/SIRT1 signaling pathway involved in black raspberry anthocyanin colorectal cancer chemoprevention / 中草药

ABSTRACT

Objective To investigate the role of miR-338-5p/SIRT1-related signaling pathway in the treatment of colorectal cancer by the chemopreventive effects of black raspberry (BRB) anthocyanins. Methods Mice were divided into normal healthy control group, AOM/DSS-induced colorectal cancer groups with or without BRB anthocyanin. miRNA microarray was used to investigate differentially expressed miRNAs and RT-qPCR was applied to verify the expression of selected miR-338-5p/SIRT1 in colon tissue of mice and human colorectal cancer cell lines of Caco-2, LoVo, HCT-116, HT29, and SW480. TargetScan and miRanda bioinformatics software was used to predict the targeted regulation relationships between miR-338-5p and SIRT1. The expression of SIRT1 protein in colon tissue of mice and downstream signaling pathway-related proteins were determined by Western blotting. Results miRNA microarray differential analysis demonstrated that the expression of miR-338-5p was significantly reduced in colon tissues of AOM/DSS induced mice fed with BRB anthocyanin. While after 9 weeks administration of BRB anthocyanins, the level of miR- 338-5p in AOM/DSS induced mice was decreased. The expression pattern of miR-338-5p was confirmed in the colon tissue and several colon cancer cell lines. Meanwhile, colorectal cancer cells were treated with BRB anthocyanin, miR-338-5p expression was reduced. TargetScan and miRanda predicted that the SIRT1 was one of target genes of miR-338-5p. BRB anthocyanins could promote the expression of SIRT1 protein in intestinal epithelial cells and regulate the protein levels of downstream moleculars including mTOR et al. Conclusion miR-338-5p/SIRT1-related signaling pathway might involve in the chemoprevention effects of BRB anthocyanin on colorectal cancer, which provided a new strategy for chemoprevention of colorectal cancer.