ReferenceID 3958
p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma
Cancer Lett
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
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Record Fields
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- Reference Id
- 3958
- Evidence Id
- 20548
- Core Evidence Id
- 20548
- Source Reference Id
- 1195
- Herb2 Reference Id
- HBREF001992
- Subject Paper Key
- HBIN043028_31163195
- Pubmed Id
- 31163195
- Doi
- 10.1016/j.canlet.2019.05.042
- Paper Title
- p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma
- Paper Abstract
- 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.
- Journal
- Cancer Lett
- Publish Year
- 2019
- Experiment Subject
- hcc cells with wildtype or mutated
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma
- Bilingual Status
- semi_complete