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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.
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To explore the serum miR-338-5p expression characteristics in renal transplant recipients ,and the role of regulating BAFF signal ,then investigate its biological significance.Methods:Healthy volunteers were enrolled as control group.Serum miR-338-5p was detected by real-time PCR;soluble BAFF was detected by ELISA;anti-HLA-Ⅰantibody,anti-HLA-Ⅱ antibody and anti-MICA antibody were detected by liquid chip technology.SPSS17.0 software was applied.t-test was used to compare the means of two independent samples;Paired samples t-test was used to compare the means of two paired samples;Spearman method and Pearson method were used to analyse the correlation;P<0.05 was considered to be statistically significant.Results: Compared with healthy controls,serum miR-338-5p in renal transplant recipients decreased significantly (P<0.001),while serum BAFF increased significantly (P<0.01).Serum miR-338-5p levels within 1 year post-transplantation were significantly lower than that of more than 1 year post-transplantation (P<0.01);Serum miR-338-5p levels within 3 years post-transplantation were significantly lower than that of more than 3 years post-transplantation (P<0.01);To all research objects,serum miR-338-5p was significantly negatively correlated with serum BAFF (r=-0.51,P<0.001),and serum miR-338-5p was significantly negatively correlated with anti-HLA-Ⅱ antibody(r=-0.322, P<0.05);Serum miR-338-5p within 3 years was significantly negatively correlated with anti-HLA-Ⅱantibody (r=-0.423,P<0.05), and serum miR-338-5p within 3 years was significantly negatively correlated with anti-MICA antibody(r=-0.411,P<0.05);Serum miR-338-5p more than 3 years was significantly positively correlated with anti-MICA antibody(r=0.486,P<0.05),and Serum miR-338-5p more than 3 years was significantly positively correlated with anti-HLA & MICA antibody(r=0.578,P<0.01).Conclusion:miR-338-5p may directly or indirectly target BAFF signal ,and participate antibody mediated immune response by regulating its target genes and interfere with the long-term survival of transplanted renal.