p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma.

MicroRNAs (miRNAs) were involved in cancer progression, and the targeting of miRNAs by natural agents has opened avenues for cancer treatment and drug development. miR-16 functions as a tumor suppressor and is frequently deleted or downregulated in various human cancers, including hepatocellular carcinoma (HCC). In the present study, we employed a miR-16-responsive luciferase reporter to screen candidate compounds that modulate miR-16 expression from a natural product library. One compound, sanguinarine (SG), was capable of activating miR-16 in HCC cells with wildtype or mutated p53 expression but not in p53-deleted HCC cells. Mechanistic investigations revealed that SG increased p53 occupancy on the miR-16-2 promoter and decreased the expression of miR-16 target genes, including Bcl-2 and cyclin D1. Moreover, SG significantly inhibited HCC cell proliferation in a p53-dependent manner by inducing cell cycle arrest and reactive oxygen species (ROS)-associated apoptosis. Silencing miR-16 by treatment with anti-miR16 miRNA inhibitors rescued the cell viability repression effect caused by SG. Importantly, SG dramatically suppressed tumor growth in an HCC xenograft model, with little cytotoxicity. Taken together, our results provide a preclinical proof-of-concept for SG as a potential strategy for HCC treatment based on the restoration of miR-16 tumor suppressor function.

[Isolation and identification of bacteria with ferro-oxidase activity].

OBJECTIVE: We screened and isolated Ferro-oxidase producing bacteria, for adsorbing iron and manganese. METHOD: The strains producing Ferro-oxidase were isolated from three samples of water. Ferro-oxidase producing strains were screened in shake flask culture, and identified according to morphological features, physiological and biochemical analysis as well as 16S rRNA gene sequence analysis. RESULTS: We isolated a bacterium S9. The strain was identified as Sphaerotilus natans. This strain had strongest adsorption on iron and manganese among the strains we identified, with 29.02 mg/g iron adsorption amount in water, and 66.77% adsorption rate for 4 hours' adsorption. When the adsorption time is 6 h, the adsorption amount of manganese was 34.49 mg/g, and the adsorption rate was 70.68%. The optimum temperature and pH value of Ferro-oxidase were 30 degrees C and 7.5, respectively. Mg2+, Na+, K+ could activate Ferro-oxidase, whereas Cu2+ had little impact. While Mn2+, Zn2+ could strongly inhibit Ferro-Oxidase, Pb2+, Ag+ had only modest inhibitory effect. CONCLUSION: Strain S9 had a high Ferro-oxidase activity, and has application potential in sewage treatment.